Variant 1-2591922-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033467.4(MMEL1):c.2163+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,610,910 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 3 hom. )

Consequence

MMEL1
NM_033467.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.03

Variant links:

Genes affected

MMEL1 (HGNC:14668): (membrane metalloendopeptidase like 1) The protein encoded by this gene is a member of the neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mainly in testis with weak expression in the brain, kidney, and heart. [provided by RefSeq, Jul 2008]

MMEL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 1-2591922-C-T is Benign according to our data. Variant chr1-2591922-C-T is described in ClinVar as [Benign]. Clinvar id is 719937.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMEL1	NM_033467.4 linkuse as main transcript	c.2163+10G>A		intron_variant		ENST00000378412.8	NP_258428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMEL1	ENST00000378412.8 linkuse as main transcript	c.2163+10G>A		intron_variant		2	NM_033467.4	ENSP00000367668	P1	Q495T6-1

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

315

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00454

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00141

AC:

354

AN:

250380

Hom.:

AF XY:

0.00131

AC XY:

177

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00431

Gnomad EAS exome

AF:

0.00501

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000876

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000841

AC:

1226

AN:

1458634

Hom.:

Cov.:

AF XY:

0.000834

AC XY:

605

AN XY:

725754

show subpopulations

Gnomad4 AFR exome

AF:

0.00359

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.00476

Gnomad4 EAS exome

AF:

0.00312

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.000379

Gnomad4 NFE exome

AF:

0.000648

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152276

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00452

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00227

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0010

DANN

Benign

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over