NM_138694.4(PKHD1):c.9577G>A (p.Val3193Ile) AND not provided

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Jun 23, 2020
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:: RCV000224330.7

Allele description [Variation Report for NM_138694.4(PKHD1):c.9577G>A (p.Val3193Ile)]

NM_138694.4(PKHD1):c.9577G>A (p.Val3193Ile)

Gene:

PKHD1:PKHD1 ciliary IPT domain containing fibrocystin/polyductin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p12.3

Genomic location:

Preferred name:

NM_138694.4(PKHD1):c.9577G>A (p.Val3193Ile)

HGVS:

NC_000006.12:g.51748039C>T
NG_008753.1:g.344587G>A
NM_138694.4:c.9577G>AMANE SELECT
NM_170724.3:c.9577G>A
NP_619639.3:p.Val3193Ile
NP_733842.2:p.Val3193Ile
NC_000006.11:g.51612837C>T
NM_138694.3:c.9577G>A

Protein change:

V3193I

Links:

dbSNP: rs35445653

NCBI 1000 Genomes Browser:

rs35445653

Molecular consequence:

NM_138694.4:c.9577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170724.3:c.9577G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000281399	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Sep 29, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000699887	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 9, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15805161, 15698423 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001897380	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Jun 23, 2020)	germline	clinical testing	Citation Link,
SCV005226124	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign	germline	not provided	PubMed (1) [See all records that cite this PMID]

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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	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, not provided
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts.

Sharp AM, Messiaen LM, Page G, Antignac C, Gubler MC, Onuchic LF, Somlo S, Germino GG, Guay-Woodford LM.

J Med Genet. 2005 Apr;42(4):336-49. No abstract available.

PubMed [citation]

PMID:: 15805161
PMCID:: PMC1736033

Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD).

Bergmann C, Senderek J, Windelen E, Küpper F, Middeldorf I, Schneider F, Dornia C, Rudnik-Schöneborn S, Konrad M, Schmitt CP, Seeman T, Neuhaus TJ, Vester U, Kirfel J, Büttner R, Zerres K; APN (Arbeitsgemeinschaft für Pädiatrische Nephrologie)..

Kidney Int. 2005 Mar;67(3):829-48.

PubMed [citation]

PMID:: 15698423

See all PubMed Citations (3)

Details of each submission

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000281399.1

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

#	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	0.003924	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699887.1

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

Description

Variant summary: The PKHD1 c.9577G>A (p.Val3193Ile) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant. This variant was found in 720/121508 control chromosomes (including 12 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0612736 (637/10396). This frequency is about 9 times the estimated maximal expected allele frequency of a pathogenic PKHD1 variant (0.0070711). As this variant exceeds allele frequency of 5% in African population, it can be regarded a common benign polymorphism found in the populations of African origin. It has also been published as a polymorphism in literature from in a ARPKD patient/normal controls (Sharp_2005). In addition, multiple clinical diagnostic laboratories have classified this variant as benign. Taken together, this variant is classified as Benign.

#	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

From GeneDx, SCV001897380.1

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

Description

This variant is associated with the following publications: (PMID: 15698423)

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

From Breakthrough Genomics, Breakthrough Genomics, SCV005226124.1

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

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

Last Updated: Sep 29, 2024

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