NM_003661.4(APOL1):c.1164_1169del (p.Asn388_Tyr389del) AND Focal segmental glomerulosclerosis 4, susceptibility to

Germline classification:: Likely risk allele; risk factor (3 submissions)
Last evaluated:: Mar 24, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000006454.9

Allele description [Variation Report for NM_003661.4(APOL1):c.1164_1169del (p.Asn388_Tyr389del)]

NM_003661.4(APOL1):c.1164_1169del (p.Asn388_Tyr389del)

Gene:

APOL1:apolipoprotein L1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_003661.4(APOL1):c.1164_1169del (p.Asn388_Tyr389del)

HGVS:

NC_000022.10:g.36662042_36662047del
NC_000022.11:g.36266000_36266005del
NG_023228.1:g.17930_17935del
NM_001136540.2:c.1164_1169del
NM_001136541.2:c.1110_1115del
NM_001362927.2:c.1110_1115del
NM_003661.4:c.1164_1169delMANE SELECT
NM_145343.3:c.1212_1217del
NP_001130012.1:p.Asn388_Tyr389del
NP_001130013.1:p.Asn370_Tyr371del
NP_001349856.1:p.Asn370_Tyr371del
NP_003652.2:p.Asn388_Tyr389del
NP_663318.1:p.Asn404_Tyr405del
LRG_169:g.17930_17935del
NC_000022.10:g.36662042_36662047del
NC_000022.10:g.36662046_36662051del
NC_000022.10:g.36662046_36662051delTTATAA
NC_000022.11:g.36265996_36266001delATAATT
NM_003661.3:c.1160_1165del
NM_003661.3:c.1164_1169delTTATAA
NM_003661.4:c.1164_1169delTTATAAMANE SELECT
NM_145343.2:c.1212_1217delTTATAA
c.1164_1169delTTATAA (p.Asn388_Tyr389del)

Links:

OMIM: 603743.0002; dbSNP: rs71785313

NCBI 1000 Genomes Browser:

rs71785313

Molecular consequence:

NM_001136540.2:c.1164_1169del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001136541.2:c.1110_1115del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001362927.2:c.1110_1115del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_003661.4:c.1164_1169del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_145343.3:c.1212_1217del - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Name:: Focal segmental glomerulosclerosis 4, susceptibility to (FSGS4)
Identifiers:: MONDO: MONDO:0012931; MedGen: C2675525; Orphanet: 84271; OMIM: 612551

Recent activity

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PREDICTED: Rattus norvegicus ubiquitin C-terminal hydrolase L1 (Uchl1), transcri...
PREDICTED: Rattus norvegicus ubiquitin C-terminal hydrolase L1 (Uchl1), transcript variant X1, mRNA
gi|2678894653|ref|XM_063273003.1|

Nucleotide
PREDICTED: Rattus norvegicus ubiquitin C-terminal hydrolase L1 (Uchl1), transcri...
PREDICTED: Rattus norvegicus ubiquitin C-terminal hydrolase L1 (Uchl1), transcript variant X2, mRNA
gi|2678894655|ref|XM_063273004.1|

Nucleotide
DDB1- and CUL4-associated factor 5 [Rattus norvegicus]
DDB1- and CUL4-associated factor 5 [Rattus norvegicus]
gi|291042683|ref|NP_001094188.1|

Protein
ubiquitin carboxyl-terminal hydrolase isozyme L1 isoform X2 [Rattus norvegicus]
ubiquitin carboxyl-terminal hydrolase isozyme L1 isoform X2 [Rattus norvegicus]
gi|2678894656|ref|XP_063129074.1|

Protein
SRX10016435 (1)
SRA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026637	OMIM	no assertion criteria provided	risk factor (Aug 13, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000924397	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	risk factor (Feb 27, 2015)	unknown, biparental	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20647424, 25741868
SCV002518488	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Likely risk allele (Mar 24, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000026637

OMIM

no assertion criteria provided

risk factor
(Aug 13, 2010)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000924397

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

risk factor
(Feb 27, 2015)

unknown, biparental

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002518488

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Likely risk allele
(Mar 24, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	biparental	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	biparental	no	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	no	2	not provided	not provided	2	not provided	clinical testing

Citations

PubMed

Association of trypanolytic ApoL1 variants with kidney disease in African Americans.

Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR.

Science. 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032. Epub 2010 Jul 15.

PubMed [citation]

PMID:: 20647424
PMCID:: PMC2980843

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000026637.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an association analysis comparing 205 African Americans with biopsy-proven focal segmental glomerulosclerosis (FSGS4; 612551) and no family history of FSGS with 180 African American controls, Genovese et al. (2010) identified association with FSGS of a 6-bp deletion, rs71785313, which they termed allele G2, in the last exon of the APOL1 gene. This mutation resulted in the deletion of 6 basepairs and removal of amino acids asparagine-388 (N388) and tyrosine-389 (Y389). The G2 allele was detected in 3 Yoruban participants but not in any patients from Europe, Japan, or China, all from HapMap 1000 Genomes data. The 6-bp deletion occurs at the SRA binding site in the APOL1 C-terminal helix. Genovese et al. (2010) showed that human plasma samples and recombinant APOL1 protein carrying the G2 allele lysed both SRA-negative and SRA-positive T. b. rhodesiense parasites, but not T. b. gambiense.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV000924397.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)
2	not provided	1	not provided	not provided	clinical testing	PubMed (2)
3	not provided	1	not provided	not provided	clinical testing	PubMed (2)
4	not provided	1	not provided	not provided	clinical testing	PubMed (2)
5	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

G2/wild type; identical twin sister with end-stage renal disease, this individual tested as part of a living donor workup

G2/wild type; sickle cell anemia

G2/G2

G2/wild type; tested as a candidate donor for affected brother (individual in line 26)

G1/G2; mother and brother with end stage renal disease of unknown cause, tested as part of a living donor workup.

Description

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	no	1	not provided	not provided		1	not provided	not provided	not provided
2	unknown	unknown	1	not provided	not provided		1	not provided	not provided	not provided
3	biparental	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	unknown	no	1	not provided	not provided		1	not provided	not provided	not provided
5	biparental	no	1	not provided	not provided		1	not provided	not provided	not provided

From Mendelics, SCV002518488.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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