11-122867553-A-T

Variant names:

• chr11-122867553-A-T
• rs2272094
• NM_019604.4:c.962A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019604.4(CRTAM):​c.962A>T​(p.Lys321Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRTAM NM_019604.4 missense, splice_region
• Scores: Splicing: ADA: 0.007318
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672
• Publications: 40 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAM	NM_019604.4	c.962A>T	p.Lys321Ile	missense_variant, splice_region_variant	Exon 8 of 10	ENST00000227348.9	NP_062550.2
CRTAM	NM_001304782.2	c.365A>T	p.Lys122Ile	missense_variant, splice_region_variant	Exon 3 of 5		NP_001291711.1
CRTAM	XM_011542900.3	c.809A>T	p.Lys270Ile	missense_variant, splice_region_variant	Exon 7 of 9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9	c.962A>T	p.Lys321Ile	missense_variant, splice_region_variant	Exon 8 of 10	1	NM_019604.4	ENSP00000227348.4
CRTAM	ENST00000533709.1	c.365A>T	p.Lys122Ile	missense_variant, splice_region_variant	Exon 3 of 5	1		ENSP00000433728.1
CRTAM	ENST00000533416.1	n.274A>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460736 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 726540

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111452

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.0074	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.9	L;.
PhyloP100		0.67
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.99	D;D
Vest4		0.46
MutPred		0.32		Loss of methylation at K321 (P = 0.0011);.;
MVP		0.58
MPC		0.49
ClinPred		0.98	D
GERP RS		-2.5
Varity_R		0.34
gMVP		0.38
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0073
dbscSNV1_RF	Benign	0.37
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

Other links and lift over

dbSNP: rs2272094; hg19: chr11-122738261;