Variant 1-160841315-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016382.4(CD244):c.550G>A(p.Val184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD244
NM_016382.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

Variant links:

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]

CD244 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031422734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD244	NM_016382.4 linkuse as main transcript	c.550G>A	p.Val184Ile	missense_variant	3/9	ENST00000368034.9	NP_057466.1	Q9BZW8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD244	ENST00000368034.9 linkuse as main transcript	c.550G>A	p.Val184Ile	missense_variant	3/9	1	NM_016382.4	ENSP00000357013.4	Q9BZW8-2
CD244	ENST00000368033.7 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	3/9	1		ENSP00000357012.3	Q9BZW8-1
CD244	ENST00000322302.7 linkuse as main transcript	c.379+269G>A		intron_variant		1		ENSP00000313619.7	Q9BZW8-4
CD244	ENST00000492063.5 linkuse as main transcript	n.550G>A		non_coding_transcript_exon_variant	3/9	2		ENSP00000432636.1	Q9BZW8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251454

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0060

DANN

Benign

0.17

DEOGEN2

Benign

0.072

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.65

.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.013

Sift

Benign

0.90

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.010

B;B

Vest4

0.058

MutPred

0.29

.;Loss of loop (P = 0.1242);

MVP

0.072

MPC

0.059

ClinPred

0.035

GERP RS

-4.0

Varity_R

0.024

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over