7-141943945-G-T

Position:

• chr7-141943945-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013252.3(CLEC5A):​c.159C>A​(p.Ser53Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,252 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: 6.9e-7 (0 hom.)
• Consequence: CLEC5A NM_013252.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.493

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]

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]

CLEC5A (HGNC:):

ACMG classification

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=0.042326987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC5A	NM_013252.3	c.159C>A	p.Ser53Arg	missense_variant	4/7	ENST00000546910.6	NP_037384.1
CLEC5A	NM_001301167.2	c.139+1396C>A		intron_variant			NP_001288096.1
CLEC5A	XM_011515995.3	c.79+2269C>A		intron_variant			XP_011514297.1
CLEC5A	XR_007059995.1	n.347C>A		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC5A	ENST00000546910.6	c.159C>A	p.Ser53Arg	missense_variant	4/7	1	NM_013252.3	ENSP00000449999.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457252 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725114

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.159C>A (p.S53R) alteration is located in exon 4 (coding exon 3) of the CLEC5A gene. This alteration results from a C to A substitution at nucleotide position 159, causing the serine (S) at amino acid position 53 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.3
DANN	Benign	0.48
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.75	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.0050
Sift	Benign	0.35	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.20		Loss of glycosylation at S53 (P = 0.0503);
MVP		0.12
MPC		0.095
ClinPred		0.053	T
GERP RS		-1.7
Varity_R		0.031
gMVP		0.41

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.

Other links and lift over

hg19: chr7-141643745;