7-141935897-A-T

Position:

chr7-141935897-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013252.3(CLEC5A):c.262T>A(p.Ser88Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,460,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

CLEC5A
NM_013252.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

CLEC5A (HGNC:2054): (C-type lectin domain containing 5A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined. [provided by RefSeq, Jul 2008]

CLEC5A links:

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

MGAM links:

CLEC5A (HGNC:):

CLEC5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.04308948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC5A	NM_013252.3 linkuse as main transcript	c.262T>A	p.Ser88Thr	missense_variant	5/7	ENST00000546910.6	NP_037384.1	Q9NY25-1A4D1U7
CLEC5A	NM_001301167.2 linkuse as main transcript	c.193T>A	p.Ser65Thr	missense_variant	4/6		NP_001288096.1	Q14DL9
CLEC5A	XM_011515995.3 linkuse as main transcript	c.133T>A	p.Ser45Thr	missense_variant	3/5		XP_011514297.1
CLEC5A	XR_007059995.1 linkuse as main transcript	n.450T>A		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC5A	ENST00000546910.6 linkuse as main transcript	c.262T>A	p.Ser88Thr	missense_variant	5/7	1	NM_013252.3	ENSP00000449999.1		Q9NY25-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251340

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1460734

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Feb 16, 2023

The c.262T>A (p.S88T) alteration is located in exon 5 (coding exon 4) of the CLEC5A gene. This alteration results from a T to A substitution at nucleotide position 262, causing the serine (S) at amino acid position 88 to be replaced by a threonine (T). 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

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.049

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.33

N;N;N

REVEL

Benign

0.058

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.11

MutPred

0.44

Loss of disorder (P = 0.0774);.;.;

MVP

0.21

MPC

0.079

ClinPred

0.040

GERP RS

-3.3

Varity_R

0.28

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over