3-136863111-C-T

Variant names:

• chr3-136863111-C-T
• rs938525
• NM_001291999.2:c.-19+758C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291999.2(NCK1):​c.-19+758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,866 control chromosomes in the GnomAD database, including 35,271 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35271 hom., cov: 31)
• Consequence: NCK1 NM_001291999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

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.-19+758C>T		intron	N/A	NP_001278928.1	P16333-1
	NCK1	NM_006153.6		c.-19+792C>T		intron	N/A	NP_006144.1	P16333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCK1	ENST00000481752.6	TSL:5 MANE Select	c.-19+758C>T		intron	N/A	ENSP00000417273.1	P16333-1
	NCK1	ENST00000288986.6	TSL:1	c.-19+792C>T		intron	N/A	ENSP00000288986.2	P16333-1
	NCK1	ENST00000951211.1		c.-19+792C>T		intron	N/A	ENSP00000621270.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102977 AN: 151750 Hom.: 35255 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.678 AC: 103027 AN: 151866 Hom.: 35271 Cov.: 31 AF XY: 0.682 AC XY: 50599 AN XY: 74230

African (AFR) AF: 0.605 AC: 25023 AN: 41354

American (AMR) AF: 0.740 AC: 11307 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2441 AN: 3470

East Asian (EAS) AF: 0.868 AC: 4490 AN: 5174

South Asian (SAS) AF: 0.742 AC: 3563 AN: 4804

European-Finnish (FIN) AF: 0.671 AC: 7056 AN: 10514

Middle Eastern (MID) AF: 0.724 AC: 210 AN: 290

European-Non Finnish (NFE) AF: 0.692 AC: 47021 AN: 67972

Other (OTH) AF: 0.680 AC: 1432 AN: 2106

Alfa AF: 0.685 Hom.: 12432

Bravo AF: 0.680

Asia WGS AF: 0.794 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.7
DANN	Benign	0.92
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs938525; hg19: chr3-136581953;