11-122850176-C-A

Variant names:

• chr11-122850176-C-A
• NM_019604.4:c.155C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019604.4(CRTAM):​c.155C>A​(p.Thr52Asn) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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]

ENSG00000285909 (HGNC:):

ACMG classification

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=0.043264985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAM	NM_019604.4	c.155C>A	p.Thr52Asn	missense_variant	Exon 2 of 10	ENST00000227348.9	NP_062550.2
CRTAM	XM_011542900.3	c.155C>A	p.Thr52Asn	missense_variant	Exon 2 of 9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9	c.155C>A	p.Thr52Asn	missense_variant	Exon 2 of 10	1	NM_019604.4	ENSP00000227348.4
ENSG00000285909	ENST00000649590.1	n.73+1369G>T		intron_variant	Intron 1 of 6

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

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.155C>A (p.T52N) alteration is located in exon 2 (coding exon 2) of the CRTAM gene. This alteration results from a C to A substitution at nucleotide position 155, causing the threonine (T) at amino acid position 52 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.32	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.46	T
Polyphen		0.0060	B
Vest4		0.11
MutPred		0.38		Loss of catalytic residue at S54 (P = 0.221);
MVP		0.47
MPC		0.088
ClinPred		0.32	T
GERP RS		5.3
Varity_R		0.17
gMVP		0.55

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: chr11-122720884;