rs1569536504

Variant names:

• chr19-54906715-T-C
• rs1569536504
• NM_004829.7:c.263T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-54906715-T-C
• chr19-54906715-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004829.7(NCR1):​c.263T>C​(p.Met88Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: NCR1 NM_004829.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

NCR1 (HGNC:6731): (natural cytotoxicity triggering receptor 1) Predicted to be involved in cellular defense response; regulation of natural killer cell mediated cytotoxicity; and signal transduction. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR1	NM_004829.7	c.263T>C	p.Met88Thr	missense_variant	Exon 3 of 7	ENST00000291890.9	NP_004820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR1	ENST00000291890.9	c.263T>C	p.Met88Thr	missense_variant	Exon 3 of 7	5	NM_004829.7	ENSP00000291890.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.024	.;T;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.24	N
M_CAP	Benign	0.0036	T
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.5	D;.;.;D
REVEL	Benign	0.19
Sift	Benign	0.045	D;.;.;D
Sift4G	Uncertain	0.020	D;T;D;T
Vest4		0.72
MutPred		0.63		Gain of catalytic residue at M88 (P = 0.054);.;Gain of catalytic residue at M88 (P = 0.054);Gain of catalytic residue at M88 (P = 0.054);
MVP		0.55
MPC		0.61
ClinPred		0.59	D
GERP RS		3.7
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1569536504; hg19: chr19-55418073;