NM_033467.4:c.155-8257C>T

Variant names:

• chr1-2620461-G-A
• rs11590198
• NM_033467.4:c.155-8257C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033467.4(MMEL1):​c.155-8257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,092 control chromosomes in the GnomAD database, including 3,755 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 0.21 (3755 hom., cov: 32)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 13 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

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.155-8257C>T		intron	N/A	NP_258428.2	Q495T6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMEL1	ENST00000378412.8	TSL:2 MANE Select	c.155-8257C>T		intron	N/A	ENSP00000367668.3	Q495T6-1
	MMEL1	ENST00000502556.5	TSL:1	c.155-8257C>T		intron	N/A	ENSP00000422492.1	Q495T6-3
	MMEL1	ENST00000504800.5	TSL:2	n.155-8257C>T		intron	N/A	ENSP00000425477.1	Q495T6-2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31417 AN: 151974 Hom.: 3743 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.207 AC: 31459 AN: 152092 Hom.: 3755 Cov.: 32 AF XY: 0.215 AC XY: 16014 AN XY: 74362

African (AFR) AF: 0.171 AC: 7076 AN: 41484

American (AMR) AF: 0.282 AC: 4308 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2407 AN: 5172

South Asian (SAS) AF: 0.392 AC: 1885 AN: 4812

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10572

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12475 AN: 67974

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.192 Hom.: 9194

Bravo AF: 0.204

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.48
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

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: rs11590198; hg19: chr1-2551900;