11-122851791-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_019604.4(CRTAM):ā€‹c.292T>Gā€‹(p.Cys98Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

CRTAM
NM_019604.4 missense

Scores

9
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.99

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRTAMNM_019604.4 linkuse as main transcriptc.292T>G p.Cys98Gly missense_variant 3/10 ENST00000227348.9 NP_062550.2
CRTAMXM_011542900.3 linkuse as main transcriptc.193+1577T>G intron_variant XP_011541202.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRTAMENST00000227348.9 linkuse as main transcriptc.292T>G p.Cys98Gly missense_variant 3/101 NM_019604.4 ENSP00000227348 P1O95727-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251430
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000965
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:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsApr 23, 2024The c.292T>G (p.C98G) alteration is located in exon 3 (coding exon 3) of the CRTAM gene. This alteration results from a T to G substitution at nucleotide position 292, causing the cysteine (C) at amino acid position 98 to be replaced by a glycine (G). 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
Pathogenic
0.93
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.27
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.71
D
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.71
T
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Pathogenic
3.8
H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-12
D
REVEL
Pathogenic
0.73
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.92
Gain of disorder (P = 0.0063);
MVP
0.71
MPC
0.45
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.99
gMVP
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs750400327; hg19: chr11-122722499; API