Variant 11-61121673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014207.4(CD5):c.868G>A(p.Glu290Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CD5
NM_014207.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

Variant links:

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]

CD5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD5	NM_014207.4 linkuse as main transcript	c.868G>A	p.Glu290Lys	missense_variant	6/11	ENST00000347785.8
CD5	NM_001346456.2 linkuse as main transcript	c.697G>A	p.Glu233Lys	missense_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD5	ENST00000347785.8 linkuse as main transcript	c.868G>A	p.Glu290Lys	missense_variant	6/11	1	NM_014207.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709070

show subpopulations

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:

9.15e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.868G>A (p.E290K) alteration is located in exon 6 (coding exon 6) of the CD5 gene. This alteration results from a G to A substitution at nucleotide position 868, causing the glutamic acid (E) at amino acid position 290 to be replaced by a lysine (K). 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

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.92

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.51

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.84

MutPred

0.75

Gain of MoRF binding (P = 0.0106);

MVP

0.86

MPC

1.0

ClinPred

0.99

GERP RS

5.6

Varity_R

0.87

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over