6-46834633-G-T

Position:

• chr6-46834633-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005588.3(MEP1A):​c.1665G>T​(p.Thr555Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: MEP1A NM_005588.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82

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]

MEP1A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEP1A	NM_005588.3	c.1665G>T	p.Thr555Thr	synonymous_variant	12/14	ENST00000230588.9	NP_005579.2
MEP1A	XM_011514628.2	c.1749G>T	p.Thr583Thr	synonymous_variant	11/13		XP_011512930.1
MEP1A	XM_011514629.3	c.1665G>T	p.Thr555Thr	synonymous_variant	12/14		XP_011512931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEP1A	ENST00000230588.9	c.1665G>T	p.Thr555Thr	synonymous_variant	12/14	1	NM_005588.3	ENSP00000230588.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: 18

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4714952; hg19: chr6-46802370;