11-122850207-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019604.4(CRTAM):​c.186G>C​(p.Glu62Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Consequence

CRTAM
NM_019604.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.284
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]

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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=0.025718719).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRTAMNM_019604.4 linkuse as main transcriptc.186G>C p.Glu62Asp missense_variant 2/10 ENST00000227348.9 NP_062550.2
CRTAMXM_011542900.3 linkuse as main transcriptc.186G>C p.Glu62Asp missense_variant 2/9 XP_011541202.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRTAMENST00000227348.9 linkuse as main transcriptc.186G>C p.Glu62Asp missense_variant 2/101 NM_019604.4 ENSP00000227348 P1O95727-1
ENST00000649590.1 linkuse as main transcriptn.73+1338C>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 24, 2024The c.186G>C (p.E62D) alteration is located in exon 2 (coding exon 2) of the CRTAM gene. This alteration results from a G to C substitution at nucleotide position 186, causing the glutamic acid (E) at amino acid position 62 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
Benign
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
14
DANN
Benign
0.67
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.82
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.41
N
REVEL
Benign
0.099
Sift
Benign
0.93
T
Sift4G
Benign
0.46
T
Polyphen
0.0
B
Vest4
0.090
MutPred
0.39
Gain of ubiquitination at K67 (P = 0.1504);
MVP
0.15
MPC
0.061
ClinPred
0.030
T
GERP RS
-0.27
Varity_R
0.30
gMVP
0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-122720915; API