rs193921024

Variant names:

• chr1-160832565-C-T
• rs193921024
• NM_016382.4:c.971G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016382.4(CD244):​c.971G>A​(p.Arg324Lys) 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 (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD244 NM_016382.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.237
• Publications: 0 publications found

Genes affected

CD244 (HGNC:18171): (CD244 molecule) This gene encodes a cell surface receptor expressed on natural killer (NK) cells (and some T cells) that mediate non-major histocompatibility complex (MHC) restricted killing. The interaction between NK-cell and target cells via this receptor is thought to modulate NK-cell cytolytic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028683662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016382.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD244	NM_016382.4	MANE Select	c.971G>A	p.Arg324Lys	missense	Exon 8 of 9	NP_057466.1
	CD244	NM_001166663.2		c.986G>A	p.Arg329Lys	missense	Exon 8 of 9	NP_001160135.1
	CD244	NM_001166664.2		c.695G>A	p.Arg232Lys	missense	Exon 7 of 8	NP_001160136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD244	ENST00000368034.9	TSL:1 MANE Select	c.971G>A	p.Arg324Lys	missense	Exon 8 of 9	ENSP00000357013.4
	CD244	ENST00000368033.7	TSL:1	c.986G>A	p.Arg329Lys	missense	Exon 8 of 9	ENSP00000357012.3
	CD244	ENST00000322302.7	TSL:1	c.695G>A	p.Arg232Lys	missense	Exon 7 of 8	ENSP00000313619.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.67
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.24
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.046
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0080	B
Vest4		0.14
MutPred		0.12		Gain of methylation at R329 (P = 0.0932)
MVP		0.12
MPC		0.067
ClinPred		0.041	T
GERP RS		1.8
Varity_R		0.043
gMVP		0.094
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs193921024; hg19: chr1-160802355; COSMIC: COSV54437397; COSMIC: COSV54437397;