1-160831382-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016382.4(CD244):c.1063C>T(p.Arg355Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00133 in 1,614,104 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00077 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (35 hom.)
• Consequence: CD244 NM_016382.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.72

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056087077).
• BP6: Variant 1-160831382-G-A is Benign according to our data. Variant chr1-160831382-G-A is described in ClinVar as [Benign]. Clinvar id is 3037210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000768 (117/152326) while in subpopulation SAS AF= 0.0199 (96/4830). AF 95% confidence interval is 0.0167. There are 3 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD244	NM_016382.4	c.1063C>T	p.Arg355Cys	missense_variant	9/9	ENST00000368034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD244	ENST00000368034.9	c.1063C>T	p.Arg355Cys	missense_variant	9/9	1	NM_016382.4	P2
CD244	ENST00000368033.7	c.1078C>T	p.Arg360Cys	missense_variant	9/9	1		A2
CD244	ENST00000322302.7	c.787C>T	p.Arg263Cys	missense_variant	8/8	1
CD244	ENST00000492063.5	c.*217C>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152208 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00273 AC: 685 AN: 251146 Hom.: 9 AF XY: 0.00377 AC XY: 512 AN XY: 135744

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0214

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.00139 AC: 2035 AN: 1461778 Hom.: 35 Cov.: 30 AF XY: 0.00194 AC XY: 1408 AN XY: 727198

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000170

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.000768 AC: 117 AN: 152326 Hom.: 3 Cov.: 33 AF XY: 0.00119 AC XY: 89 AN XY: 74492

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000301 Hom.: 1

Bravo AF: 0.000268

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00282 AC: 343

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CD244-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	26
Dann	Pathogenic	1.0
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;D;D
MetaRNN	Benign	0.0056	T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.26
MVP		0.63
MPC		0.46
ClinPred		0.065	T
GERP RS		3.7
Varity_R		0.29
gMVP		0.21

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: rs140746142; hg19: chr1-160801172; COSMIC: COSV54432063; COSMIC: COSV54432063;