rs10752747

chr1-2593476-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033467.4(MMEL1):c.1867+338C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,084 control chromosomes in the GnomAD database, including 13,940 homozygotes. 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 0.41 (13940 hom., cov: 33)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMEL1	NM_033467.4	c.1867+338C>A		intron_variant		ENST00000378412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMEL1	ENST00000378412.8	c.1867+338C>A		intron_variant		2	NM_033467.4	P1
MMEL1	ENST00000502556.5	c.1396+338C>A		intron_variant		1
MMEL1	ENST00000504800.5	c.*60+338C>A		intron_variant, NMD_transcript_variant		2
MMEL1	ENST00000469962.1	n.260+338C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62724 AN: 151968 Hom.: 13912 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.374

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 62801 AN: 152084 Hom.: 13940 Cov.: 33 AF XY: 0.417 AC XY: 30993 AN XY: 74356

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.380

Alfa AF: 0.337 Hom.: 11359

Bravo AF: 0.418

Asia WGS AF: 0.577 AC: 2007 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.9
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs10752747; hg19: chr1-2524915;