rs1059276

Positions:

• chr6-46839303-C-A
• chr6-46839303-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005588.3(MEP1A):​c.*167C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 540,010 control chromosomes in the GnomAD database, including 105,411 homozygotes. 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 0.63 (30437 hom., cov: 29)
  • Exomes 𝑓: 0.62 (74974 hom.)
• Consequence: MEP1A NM_005588.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

Genes affected

MEP1A (HGNC:7015): (meprin A subunit alpha) Predicted to enable metalloendopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. Part of meprin A complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEP1A	NM_005588.3	c.*167C>A		3_prime_UTR_variant	14/14	ENST00000230588.9
MEP1A	XM_011514628.2	c.*167C>A		3_prime_UTR_variant	13/13
MEP1A	XM_011514629.3	c.2084+3754C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEP1A	ENST00000230588.9	c.*167C>A		3_prime_UTR_variant	14/14	1	NM_005588.3	P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95366 AN: 151074 Hom.: 30398 Cov.: 29

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.618 AC: 240101 AN: 388820 Hom.: 74974 Cov.: 5 AF XY: 0.622 AC XY: 125221 AN XY: 201370

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.724

Gnomad4 ASJ exome AF: 0.693

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.631 AC: 95455 AN: 151190 Hom.: 30437 Cov.: 29 AF XY: 0.629 AC XY: 46455 AN XY: 73800

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.639

Alfa AF: 0.510 Hom.: 1355

Bravo AF: 0.637

Asia WGS AF: 0.655 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.35

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

Other links and lift over

dbSNP: rs1059276; hg19: chr6-46807040;