6-46825438-G-A

Variant names:

• chr6-46825438-G-A
• rs6920863
• NM_005588.3:c.723G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005588.3(MEP1A):​c.723G>A​(p.Gln241Gln) 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005588.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEP1A	NM_005588.3	MANE Select	c.723G>A	p.Gln241Gln	synonymous	Exon 8 of 14	NP_005579.2	Q16819

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEP1A	ENST00000230588.9	TSL:1 MANE Select	c.723G>A	p.Gln241Gln	synonymous	Exon 8 of 14	ENSP00000230588.4	Q16819
	MEP1A	ENST00000611727.2	TSL:1	c.807G>A	p.Gln269Gln	synonymous	Exon 7 of 13	ENSP00000480465.1	B7ZL91
	MEP1A	ENST00000879644.1		c.792G>A	p.Gln264Gln	synonymous	Exon 9 of 15	ENSP00000549703.1

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

GnomAD2 exomes AF: 0.395 AC: 99012 AN: 250786 AF XY: 0.392

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 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

African (AFR) AF: 0.510 AC: 17068 AN: 33436

American (AMR) AF: 0.453 AC: 20221 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10621 AN: 26108

East Asian (EAS) AF: 0.193 AC: 7650 AN: 39670

South Asian (SAS) AF: 0.404 AC: 34853 AN: 86184

European-Finnish (FIN) AF: 0.389 AC: 20753 AN: 53392

Middle Eastern (MID) AF: 0.453 AC: 2610 AN: 5762

European-Non Finnish (NFE) AF: 0.391 AC: 434100 AN: 1110730

Other (OTH) AF: 0.402 AC: 24240 AN: 60356

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

African (AFR) AF: 0.498 AC: 20625 AN: 41426

American (AMR) AF: 0.435 AC: 6633 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1351 AN: 3470

East Asian (EAS) AF: 0.188 AC: 974 AN: 5168

South Asian (SAS) AF: 0.408 AC: 1968 AN: 4820

European-Finnish (FIN) AF: 0.382 AC: 4033 AN: 10544

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27151 AN: 67950

Other (OTH) AF: 0.417 AC: 881 AN: 2112

Alfa AF: 0.400 Hom.: 14049

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.2
DANN	Benign	0.58
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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