rs2843403

chr1-2597658-T-C

Variant summary

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

The NM_033467.4(MMEL1):c.1272+549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,878 control chromosomes in the GnomAD database, including 23,897 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 0.54 (23897 hom., cov: 32)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMEL1	NM_033467.4	c.1272+549A>G		intron_variant		ENST00000378412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMEL1	ENST00000378412.8	c.1272+549A>G		intron_variant		2	NM_033467.4	P1
MMEL1	ENST00000502556.5	c.801+549A>G		intron_variant		1
MMEL1	ENST00000504800.5	c.1272+549A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82296 AN: 151758 Hom.: 23888 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.542 AC: 82323 AN: 151878 Hom.: 23897 Cov.: 32 AF XY: 0.539 AC XY: 39969 AN XY: 74216

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.587

Alfa AF: 0.589 Hom.: 4070

Bravo AF: 0.533

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.1
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs2843403; hg19: chr1-2529097;