rs10910099

Variant names:

• chr1-2602113-A-C
• rs10910099
• NM_033467.4:c.1041+1771T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-2602113-A-C
• chr1-2602113-A-G

Variant summary

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

The NM_033467.4(MMEL1):​c.1041+1771T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 150,834 control chromosomes in the GnomAD database, including 13,870 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 (13870 hom., cov: 32)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 19 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMEL1	NM_033467.4	c.1041+1771T>G		intron_variant	Intron 11 of 23	ENST00000378412.8	NP_258428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMEL1	ENST00000378412.8	c.1041+1771T>G		intron_variant	Intron 11 of 23	2	NM_033467.4	ENSP00000367668.3
MMEL1	ENST00000502556.5	c.570+1771T>G		intron_variant	Intron 6 of 18	1		ENSP00000422492.1
MMEL1	ENST00000504800.5	n.1041+1771T>G		intron_variant	Intron 10 of 22	2		ENSP00000425477.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62075 AN: 150714 Hom.: 13839 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.412 AC: 62154 AN: 150834 Hom.: 13870 Cov.: 32 AF XY: 0.416 AC XY: 30603 AN XY: 73584

African (AFR) AF: 0.563 AC: 23078 AN: 40988

American (AMR) AF: 0.433 AC: 6584 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1052 AN: 3462

East Asian (EAS) AF: 0.503 AC: 2571 AN: 5112

South Asian (SAS) AF: 0.505 AC: 2389 AN: 4734

European-Finnish (FIN) AF: 0.356 AC: 3701 AN: 10404

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21747 AN: 67638

Other (OTH) AF: 0.378 AC: 792 AN: 2096

Alfa AF: 0.365 Hom.: 4626

Bravo AF: 0.419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		0.12
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: rs10910099; hg19: chr1-2533552;