3-136863111-C-T

Position:

• chr3-136863111-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCK1	NM_001291999.2	c.-19+758C>T		intron_variant		ENST00000481752.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCK1	ENST00000481752.6	c.-19+758C>T		intron_variant		5	NM_001291999.2	P1

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

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.680

Alfa AF: 0.686 Hom.: 7315

Bravo AF: 0.680

Asia WGS AF: 0.794 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.7
DANN	Benign	0.92

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

Other links and lift over

dbSNP: rs938525; hg19: chr3-136581953;