Variant 1-2592725-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033467.4(MMEL1):c.2002-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,611,828 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 26)

Exomes 𝑓: 0.00056 ( 4 hom. )

Consequence

MMEL1
NM_033467.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008497

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.694

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-2592725-G-A is Benign according to our data. Variant chr1-2592725-G-A is described in ClinVar as [Benign]. Clinvar id is 719695.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00531 (803/151270) while in subpopulation AFR AF= 0.0188 (772/41152). AF 95% confidence interval is 0.0177. There are 7 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMEL1	NM_033467.4 linkuse as main transcript	c.2002-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, 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.2002-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_033467.4	ENSP00000367668	P1	Q495T6-1

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

802

AN:

151150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00289

GnomAD3 exomes

AF:

0.00132

AC:

329

AN:

249538

Hom.:

AF XY:

0.000947

AC XY:

128

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.000639

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000557

AC:

814

AN:

1460558

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

343

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.000874

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00531

AC:

803

AN:

151270

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

351

AN XY:

73870

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000394

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00286

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00605

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.27

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.0060

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