rs12138909

chr1-2607299-C-T

Variant summary

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

The NM_033467.4(MMEL1):c.536-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,216 control chromosomes in the GnomAD database, including 1,166 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 0.10 (1166 hom., cov: 33)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMEL1	NM_033467.4	c.536-230G>A		intron_variant		ENST00000378412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMEL1	ENST00000378412.8	c.536-230G>A		intron_variant		2	NM_033467.4	P1
MMEL1	ENST00000502556.5	c.480+2095G>A		intron_variant		1
MMEL1	ENST00000504800.5	c.536-230G>A		intron_variant, NMD_transcript_variant		2
MMEL1	ENST00000509374.1	n.365-230G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15964 AN: 152098 Hom.: 1166 Cov.: 33

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00329

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.105 AC: 15966 AN: 152216 Hom.: 1166 Cov.: 33 AF XY: 0.103 AC XY: 7652 AN XY: 74406

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.0846

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.138 Hom.: 1840

Bravo AF: 0.0969

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.54
Dann	Benign	0.58

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: rs12138909; hg19: chr1-2538738;