11-61118253-T-C

Variant names:

• chr11-61118253-T-C
• rs182453573
• NM_014207.4:c.173T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001346456.2(CD5):​c.2T>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CD5 NM_001346456.2 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602

Genes affected

CD5 (HGNC:1685): (CD5 molecule) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. This protein is a type-I transmembrane glycoprotein found on the surface of thymocytes, T lymphocytes and a subset of B lymphocytes. The encoded protein contains three SRCR domains and may act as a receptor to regulate T-cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 67 codons. Genomic position: 61118450. Lost 0.151 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD5	NM_014207.4	c.173T>C	p.Met58Thr	missense_variant	Exon 3 of 11	ENST00000347785.8	NP_055022.2
CD5	NM_001346456.2	c.2T>C	p.Met1?	start_lost	Exon 3 of 11		NP_001333385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD5	ENST00000347785.8	c.173T>C	p.Met58Thr	missense_variant	Exon 3 of 11	1	NM_014207.4	ENSP00000342681.3
CD5	ENST00000544014.1	c.173T>C	p.Met58Thr	missense_variant	Exon 3 of 5	4		ENSP00000440899.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.5
DANN	Benign	0.18
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00037	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.8	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	3.4	N;N
REVEL	Benign	0.068
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.11
MutPred		0.61		Loss of MoRF binding (P = 0.0957);Loss of MoRF binding (P = 0.0957);
MVP		0.17
MPC		0.33
ClinPred		0.055	T
GERP RS		2.1
Varity_R		0.036
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs182453573; hg19: chr11-60885725;