11-122871296-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019604.4(CRTAM):ā€‹c.1079A>Gā€‹(p.Tyr360Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

CRTAM
NM_019604.4 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29434025).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRTAMNM_019604.4 linkuse as main transcriptc.1079A>G p.Tyr360Cys missense_variant 10/10 ENST00000227348.9 NP_062550.2
CRTAMNM_001304782.2 linkuse as main transcriptc.482A>G p.Tyr161Cys missense_variant 5/5 NP_001291711.1
CRTAMXM_011542900.3 linkuse as main transcriptc.926A>G p.Tyr309Cys missense_variant 9/9 XP_011541202.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRTAMENST00000227348.9 linkuse as main transcriptc.1079A>G p.Tyr360Cys missense_variant 10/101 NM_019604.4 ENSP00000227348 P1O95727-1
CRTAMENST00000533709.1 linkuse as main transcriptc.482A>G p.Tyr161Cys missense_variant 5/51 ENSP00000433728 O95727-2
CRTAMENST00000533416.1 linkuse as main transcriptn.391A>G non_coding_transcript_exon_variant 4/45

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
250876
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135572
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000290
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:
0.0000176
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461300
Hom.:
0
Cov.:
29
AF XY:
0.0000124
AC XY:
9
AN XY:
726930
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000291
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000494
AC:
6

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 GeneticsJan 18, 2023The c.1079A>G (p.Y360C) alteration is located in exon 10 (coding exon 10) of the CRTAM gene. This alteration results from a A to G substitution at nucleotide position 1079, causing the tyrosine (Y) at amino acid position 360 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.68
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Uncertain
2.4
M;.
MutationTaster
Benign
0.97
D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;P
Vest4
0.43
MutPred
0.34
Gain of catalytic residue at M358 (P = 0.051);.;
MVP
0.65
MPC
0.45
ClinPred
0.70
D
GERP RS
3.8
Varity_R
0.59
gMVP
0.59

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.

Other links and lift over

dbSNP: rs762806413; hg19: chr11-122742004; API