Variant 11-122867415-A-G 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_019604.4(CRTAM):c.824A>G(p.Asn275Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,428 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CRTAM
NM_019604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.404

Variant links:

Genes affected

CRTAM (HGNC:24313): (cytotoxic and regulatory T cell molecule) The CRTAM gene is upregulated in CD4 (see MIM 186940)-positive and CD8 (see CD8A; MIM 186910)-positive T cells and encodes a type I transmembrane protein with V and C1-like Ig domains (Yeh et al., 2008 [PubMed 18329370]).[supplied by OMIM, Feb 2009]

CRTAM 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=0.04330519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CRTAM	NM_019604.4 linkuse as main transcript	c.824A>G	p.Asn275Ser	missense_variant	8/10	ENST00000227348.9	NP_062550.2
CRTAM	NM_001304782.2 linkuse as main transcript	c.227A>G	p.Asn76Ser	missense_variant	3/5		NP_001291711.1
CRTAM	XM_011542900.3 linkuse as main transcript	c.671A>G	p.Asn224Ser	missense_variant	7/9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9 linkuse as main transcript	c.824A>G	p.Asn275Ser	missense_variant	8/10	1	NM_019604.4	ENSP00000227348	P1	O95727-1
CRTAM	ENST00000533709.1 linkuse as main transcript	c.227A>G	p.Asn76Ser	missense_variant	3/5	1		ENSP00000433728		O95727-2
CRTAM	ENST00000533416.1 linkuse as main transcript	n.136A>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248418

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.824A>G (p.N275S) alteration is located in exon 8 (coding exon 8) of the CRTAM gene. This alteration results from a A to G substitution at nucleotide position 824, causing the asparagine (N) at amino acid position 275 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.2

DANN

Benign

0.71

DEOGEN2

Benign

0.057

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.021

Sift

Benign

0.45

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.051

B;B

Vest4

0.088

MutPred

0.22

Gain of phosphorylation at N275 (P = 0.0626);.;

MVP

0.12

MPC

0.057

ClinPred

0.029

GERP RS

0.60

Varity_R

0.034

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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