11-122850176-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043264985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019604.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAM	NM_019604.4	MANE Select	c.155C>A	p.Thr52Asn	missense	Exon 2 of 10	NP_062550.2	O95727-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAM	ENST00000227348.9	TSL:1 MANE Select	c.155C>A	p.Thr52Asn	missense	Exon 2 of 10	ENSP00000227348.4	O95727-1
	CRTAM	ENST00000910133.1		c.155C>A	p.Thr52Asn	missense	Exon 3 of 11	ENSP00000580192.1
	ENSG00000285909	ENST00000649590.1		n.73+1369G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.4
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
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

hg19: chr11-122720884;