chr3-136945965-A-T

Variant names:

• chr3-136945965-A-T
• rs61731511
• NM_001291999.2:c.609A>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.68
• Publications: 5 publications found

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]

IL20RB-AS1 (HGNC:40298): (IL20RB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCK1	NM_001291999.2	MANE Select	c.609A>T	p.Ser203Ser	synonymous	Exon 3 of 4	NP_001278928.1	P16333-1
	NCK1	NM_006153.6		c.609A>T	p.Ser203Ser	synonymous	Exon 3 of 4	NP_006144.1	P16333-1
	NCK1	NM_001190796.3		c.417A>T	p.Ser139Ser	synonymous	Exon 2 of 3	NP_001177725.1	P16333-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCK1	ENST00000481752.6	TSL:5 MANE Select	c.609A>T	p.Ser203Ser	synonymous	Exon 3 of 4	ENSP00000417273.1	P16333-1
	NCK1	ENST00000288986.6	TSL:1	c.609A>T	p.Ser203Ser	synonymous	Exon 3 of 4	ENSP00000288986.2	P16333-1
	NCK1	ENST00000951211.1		c.792A>T	p.Ser264Ser	synonymous	Exon 4 of 5	ENSP00000621270.1

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152152 Hom.: 3 Cov.: 31

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

GnomAD2 exomes AF: 0.00589 AC: 1480 AN: 251268 AF XY: 0.00595

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 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.: 72 Cov.: 32 AF XY: 0.00802 AC XY: 5830 AN XY: 727170

African (AFR) AF: 0.00131 AC: 44 AN: 33476

American (AMR) AF: 0.00680 AC: 304 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 309 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00161 AC: 139 AN: 86258

European-Finnish (FIN) AF: 0.00556 AC: 297 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00918 AC: 10205 AN: 1111886

Other (OTH) AF: 0.00797 AC: 481 AN: 60388

GnomAD4 genome AF: 0.00573 AC: 873 AN: 152270 Hom.: 3 Cov.: 31 AF XY: 0.00544 AC XY: 405 AN XY: 74470

African (AFR) AF: 0.00142 AC: 59 AN: 41540

American (AMR) AF: 0.0103 AC: 157 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00348 AC: 37 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00796 AC: 541 AN: 68006

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00352 Hom.: 2

Bravo AF: 0.00662

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-2.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs61731511; hg19: chr3-136664807;