Genetic Variant CRTAM:p.Val5Asp (chr11-122838560-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019604.4(CRTAM):c.14T>A(p.Val5Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

CRTAM
NM_019604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.420

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:

ENSG00000285909 (HGNC:):

ENSG00000285909 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAM	NM_019604.4 link	c.14T>A	p.Val5Asp	missense_variant	Exon 1 of 10	ENST00000227348.9	NP_062550.2	O95727-1
CRTAM	XM_011542900.3 link	c.14T>A	p.Val5Asp	missense_variant	Exon 1 of 9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9 link	c.14T>A	p.Val5Asp	missense_variant	Exon 1 of 10	1	NM_019604.4	ENSP00000227348.4		O95727-1
ENSG00000285909	ENST00000649590.1 link	n.73+12985A>T		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251452

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000252

AC:

369

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

181

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

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:

0.000328

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14T>A (p.V5D) alteration is located in exon 1 (coding exon 1) of the CRTAM gene. This alteration results from a T to A substitution at nucleotide position 14, causing the valine (V) at amino acid position 5 to be replaced by an aspartic acid (D). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.56

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.28

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.84

Vest4

0.77

MVP

0.30

MPC

0.14

ClinPred

0.049

GERP RS

1.3

Varity_R

0.27

gMVP

0.81

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