NM_138694.4(PKHD1):c.9469_9470delinsAA (p.Ala3157Asn) AND Autosomal recessive polycystic kidney disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000228094.7

Allele description [Variation Report for NM_138694.4(PKHD1):c.9469_9470delinsAA (p.Ala3157Asn)]

NM_138694.4(PKHD1):c.9469_9470delinsAA (p.Ala3157Asn)

Gene:

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

Variant type:

Indel

Cytogenetic location:

6p12.3

Genomic location:

Preferred name:

NM_138694.4(PKHD1):c.9469_9470delinsAA (p.Ala3157Asn)

HGVS:

NC_000006.12:g.51748146_51748147delinsTT
NG_008753.1:g.344479_344480delinsAA
NM_138694.4:c.9469_9470delinsAAMANE SELECT
NM_170724.3:c.9469_9470delinsAA
NP_619639.3:p.Ala3157Asn
NP_733842.2:p.Ala3157Asn
NC_000006.11:g.51612944_51612945delinsTT
NM_138694.3:c.9469_9470delGCinsAA

Protein change:

A3157N

Links:

dbSNP: rs878855204

NCBI 1000 Genomes Browser:

rs878855204

Molecular consequence:

NM_138694.4:c.9469_9470delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_170724.3:c.9469_9470delinsAA - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive polycystic kidney disease (ARPKD)
Synonyms:: POLYCYSTIC KIDNEY AND HEPATIC DISEASE 1; POLYCYSTIC KIDNEY DISEASE, INFANTILE, TYPE I; Polycystic kidney disease, infantile type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009889; MeSH: D017044; MedGen: C0085548; Orphanet: 731; Orphanet: 8378

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Mus musculus vacuolar protein sorting 13A (yeast), mRNA (cDNA clone IMAGE:633194...
Mus musculus vacuolar protein sorting 13A (yeast), mRNA (cDNA clone IMAGE:6331949), partial cds
gi|38566097|gb|BC062130.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000291344	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000291344

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 27, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000291344.5

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 3157 of the PKHD1 protein (p.Ala3157Asn). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 241848). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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