NM_004646.4(NPHS1):c.1638T>G (p.Thr546=) AND not provided

Clinical significance:Benign/Likely benign (Last evaluated: Jan 19, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000588114.6

Allele description [Variation Report for NM_004646.4(NPHS1):c.1638T>G (p.Thr546=)]

NM_004646.4(NPHS1):c.1638T>G (p.Thr546=)

Gene:
NPHS1:NPHS1 adhesion molecule, nephrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.12
Genomic location:
Preferred name:
NM_004646.4(NPHS1):c.1638T>G (p.Thr546=)
HGVS:
  • NC_000019.10:g.35845788A>C
  • NG_013356.2:g.28500T>G
  • NM_004646.3:c.1638T>G
  • NM_004646.4:c.1638T>GMANE SELECT
  • NP_004637.1:p.Thr546=
  • NP_004637.1:p.Thr546=
  • LRG_693t1:c.1638T>G
  • LRG_693:g.28500T>G
  • LRG_693p1:p.Thr546=
  • NC_000019.9:g.36336690A>C
Links:
dbSNP: rs115444936
NCBI 1000 Genomes Browser:
rs115444936
Molecular consequence:
  • NM_004646.3:c.1638T>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_004646.4:c.1638T>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000698498Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Oct 17, 2016)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000842913Athena Diagnostics Inccriteria provided, single submitter
Benign
(Jan 15, 2018)
germlineclinical testing

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

SCV001096571Invitaecriteria provided, single submitter
Benign
(Dec 6, 2020)
germlineclinical testing

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

SCV001981892GeneDxcriteria provided, single submitter
Likely benign
(Jan 19, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698498.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: The NPHS1 c.1638T>G (p.Thr546Thr) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC with an allele frequency of 195/119054 (1/610 including 2 homozygotes), predominantly observed in the European (Non-Finnish) cohort, 166/65658 (1/395, 1 homozygote), which does not exceed the estimated maximal expected allele frequency for a pathogenic NPHS1 variant of 1/298. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as "Likely Benign."

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Athena Diagnostics Inc, SCV000842913.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001096571.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001981892.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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