1-2629464-T-C

Variant names:

• chr1-2629464-T-C
• rs4648659
• NM_033467.4:c.21A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_033467.4(MMEL1):​c.21A>G​(p.Pro7Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000508 in 1,378,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. P7P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: MMEL1 NM_033467.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 26 publications found

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-AS1 (HGNC:40695): (MMEL1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033467.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMEL1	NM_033467.4	MANE Select	c.21A>G	p.Pro7Pro	synonymous	Exon 2 of 24	NP_258428.2	Q495T6-1
	MMEL1-AS1	NR_183343.1		n.148+561T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMEL1	ENST00000378412.8	TSL:2 MANE Select	c.21A>G	p.Pro7Pro	synonymous	Exon 2 of 24	ENSP00000367668.3	Q495T6-1
	MMEL1	ENST00000502556.5	TSL:1	c.21A>G	p.Pro7Pro	synonymous	Exon 1 of 19	ENSP00000422492.1	Q495T6-3
	MMEL1	ENST00000504800.5	TSL:2	n.21A>G		non_coding_transcript_exon	Exon 1 of 23	ENSP00000425477.1	Q495T6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000751 AC: 1 AN: 133148 AF XY: 0.0000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000508 AC: 7 AN: 1378850 Hom.: 0 Cov.: 58 AF XY: 0.0000103 AC XY: 7 AN XY: 679196

African (AFR) AF: 0.00 AC: 0 AN: 30632

American (AMR) AF: 0.00 AC: 0 AN: 34604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24468

East Asian (EAS) AF: 0.00 AC: 0 AN: 34920

South Asian (SAS) AF: 0.0000893 AC: 7 AN: 78414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070478

Other (OTH) AF: 0.00 AC: 0 AN: 57182

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.21
DANN	Benign	0.62
PhyloP100		-2.3
PromoterAI		-0.031	Neutral
Mutation Taster		=298/2	polymorphism

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

Other links and lift over

dbSNP: rs4648659; hg19: chr1-2560903;