Variant 3-136945965-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001291999.2(NCK1):c.609A>T(p.Ser203Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 1,614,016 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 72 hom. )

Consequence

NCK1
NM_001291999.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.68

Variant links:

Genes affected

NCK1 (HGNC:7664): (NCK adaptor protein 1) The protein encoded by this gene is one of the signaling and transforming proteins containing Src homology 2 and 3 (SH2 and SH3) domains. It is located in the cytoplasm and is an adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as RAS. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jun 2010]

NCK1 links:

NCK1 (HGNC:):

NCK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-136945965-A-T is Benign according to our data. Variant chr3-136945965-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3341512.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BS2

High AC in GnomAd4 at 873 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCK1	NM_001291999.2 linkuse as main transcript	c.609A>T	p.Ser203Ser	synonymous_variant	3/4	ENST00000481752.6	NP_001278928.1	P16333-1A0A0S2Z4Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCK1	ENST00000481752.6 linkuse as main transcript	c.609A>T	p.Ser203Ser	synonymous_variant	3/4	5	NM_001291999.2	ENSP00000417273.1		P16333-1

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00795

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.00589

AC:

1480

AN:

251268

Hom.:

AF XY:

0.00595

AC XY:

808

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00651

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00416

Gnomad NFE exome

AF:

0.00816

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00806

AC:

11780

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

5830

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00680

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00556

Gnomad4 NFE exome

AF:

0.00918

Gnomad4 OTH exome

AF:

0.00797

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152270

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00796

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.00662

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

NCK1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.54

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over