rs6920863

Positions:

• chr6-46825438-G-A
• chr6-46825438-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005588.3(MEP1A):​c.723G>A​(p.Gln241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,612,238 control chromosomes in the GnomAD database, including 128,087 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 0.42 (13937 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114150 hom.)
• Consequence: MEP1A NM_005588.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEP1A	NM_005588.3	c.723G>A	p.Gln241=	synonymous_variant	8/14	ENST00000230588.9
MEP1A	XM_011514628.2	c.807G>A	p.Gln269=	synonymous_variant	7/13
MEP1A	XM_011514629.3	c.723G>A	p.Gln241=	synonymous_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEP1A	ENST00000230588.9	c.723G>A	p.Gln241=	synonymous_variant	8/14	1	NM_005588.3	P1
MEP1A	ENST00000611727.2	c.807G>A	p.Gln269=	synonymous_variant	7/13	1
MEP1A	ENST00000680769.1	n.904G>A		non_coding_transcript_exon_variant	6/12
MEP1A	ENST00000680229.1	c.723G>A	p.Gln241=	synonymous_variant, NMD_transcript_variant	8/14

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64171 AN: 151822 Hom.: 13920 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.415

GnomAD3 exomes AF: 0.395 AC: 99012 AN: 250786 Hom.: 20359 AF XY: 0.392 AC XY: 53181 AN XY: 135532

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.408

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.392 AC: 572116 AN: 1460298 Hom.: 114150 Cov.: 36 AF XY: 0.392 AC XY: 285053 AN XY: 726490

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.423 AC: 64235 AN: 151940 Hom.: 13937 Cov.: 32 AF XY: 0.421 AC XY: 31246 AN XY: 74234

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.417

Alfa AF: 0.398 Hom.: 12193

Bravo AF: 0.430

Asia WGS AF: 0.366 AC: 1274 AN: 3478

EpiCase AF: 0.400

EpiControl AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.2
DANN	Benign	0.58

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: rs6920863; hg19: chr6-46793175; COSMIC: COSV57919573;