6-46835365-A-T

Variant names:

• chr6-46835365-A-T
• rs2297019
• NM_005588.3:c.1900A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005588.3(MEP1A):​c.1900A>T​(p.Met634Leu) variant causes a missense 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. 16/22 in silico tools predict 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: 32)
• Consequence: MEP1A NM_005588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 20 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049357027).

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.1900A>T	p.Met634Leu	missense	Exon 13 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.1900A>T	p.Met634Leu	missense	Exon 13 of 14	ENSP00000230588.4	Q16819
	MEP1A	ENST00000611727.2	TSL:1	c.1984A>T	p.Met662Leu	missense	Exon 12 of 13	ENSP00000480465.1	B7ZL91
	MEP1A	ENST00000879644.1		c.1969A>T	p.Met657Leu	missense	Exon 14 of 15	ENSP00000549703.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0020
DANN	Benign	0.31
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.8
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.0080
Sift	Benign	0.37	T
Sift4G	Benign	0.84	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.16		Gain of glycosylation at K632 (P = 0.2761)
MVP		0.085
MPC		0.095
ClinPred		0.091	T
GERP RS		-6.7
Varity_R		0.039
gMVP		0.27
Mutation Taster		=100/0	polymorphism

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: rs2297019; hg19: chr6-46803102;