NM_001291999.2:c.554A>C

Variant names:

• chr3-136945910-A-C
• rs1940805431
• NM_001291999.2:c.554A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001291999.2(NCK1):​c.554A>C​(p.Asn185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NCK1 NM_001291999.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18220896).

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.554A>C	p.Asn185Thr	missense	Exon 3 of 4	NP_001278928.1	P16333-1
	NCK1	NM_006153.6		c.554A>C	p.Asn185Thr	missense	Exon 3 of 4	NP_006144.1	P16333-1
	NCK1	NM_001190796.3		c.362A>C	p.Asn121Thr	missense	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.554A>C	p.Asn185Thr	missense	Exon 3 of 4	ENSP00000417273.1	P16333-1
	NCK1	ENST00000288986.6	TSL:1	c.554A>C	p.Asn185Thr	missense	Exon 3 of 4	ENSP00000288986.2	P16333-1
	NCK1	ENST00000951211.1		c.737A>C	p.Asn246Thr	missense	Exon 4 of 5	ENSP00000621270.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.064
Sift	Benign	0.10	T
Sift4G	Benign	0.54	T
Polyphen		0.049	B
Vest4		0.13
MutPred		0.39		Loss of stability (P = 0.0859)
MVP		0.83
MPC		0.56
ClinPred		0.60	D
GERP RS		6.2
Varity_R		0.10
gMVP		0.23
Mutation Taster		=71/29	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: rs1940805431; hg19: chr3-136664752;