Genetic Variant MEP1A:c.*167C>G (chr6-46839303-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005588.3(MEP1A):c.*167C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 541,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MEP1A
NM_005588.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Publications

5 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-0.82).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEP1A	NM_005588.3	MANE Select	c.*167C>G		3_prime_UTR	Exon 14 of 14	NP_005579.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MEP1A	ENST00000230588.9	TSL:1 MANE Select	c.*167C>G	3_prime_UTR	Exon 14 of 14	ENSP00000230588.4
MEP1A	ENST00000879644.1		c.*167C>G	3_prime_UTR	Exon 15 of 15	ENSP00000549703.1
MEP1A	ENST00000879647.1		c.*167C>G	3_prime_UTR	Exon 14 of 14	ENSP00000549706.1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

390664

Hom.:

Cov.:

AF XY:

0.00000494

AC XY:

AN XY:

202316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11248

American (AMR)

AF:

0.00

AC:

AN:

14442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12068

East Asian (EAS)

AF:

0.00

AC:

AN:

28318

South Asian (SAS)

AF:

0.00

AC:

AN:

28868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1736

European-Non Finnish (NFE)

AF:

0.0000206

AC:

AN:

243022

Other (OTH)

AF:

0.00

AC:

AN:

23064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151204

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73752

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41068

American (AMR)

AF:

0.00

AC:

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

1497

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

(source)

DANN

Benign

0.38

PhyloP100

0.13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over