rs547561

Variant names:

• chr11-102773163-C-T
• rs547561
• NM_002425.3:c.1067-157G>A

Variant summary

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

The NM_002425.3(MMP10):​c.1067-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,282 control chromosomes in the GnomAD database, including 67,713 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 0.94 (67713 hom., cov: 33)
• Consequence: MMP10 NM_002425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 8 publications found

Genes affected

MMP10 (HGNC:7156): (matrix metallopeptidase 10) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down fibronectin, laminin, elastin, proteoglycan core protein, gelatins, and several types of collagen. The gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

WTAPP1 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.1067-157G>A		intron_variant	Intron 7 of 9	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.1067-157G>A		intron_variant	Intron 7 of 9	1	NM_002425.3	ENSP00000279441.4
WTAPP1	ENST00000371455.7	n.324+21737C>T		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1	n.188+21737C>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143365 AN: 152164 Hom.: 67651 Cov.: 33

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.942 AC: 143486 AN: 152282 Hom.: 67713 Cov.: 33 AF XY: 0.939 AC XY: 69932 AN XY: 74446

African (AFR) AF: 0.986 AC: 40983 AN: 41566

American (AMR) AF: 0.899 AC: 13750 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3232 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4633 AN: 5180

South Asian (SAS) AF: 0.902 AC: 4351 AN: 4826

European-Finnish (FIN) AF: 0.914 AC: 9690 AN: 10598

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63757 AN: 68018

Other (OTH) AF: 0.934 AC: 1974 AN: 2114

Alfa AF: 0.937 Hom.: 109376

Bravo AF: 0.941

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.40
PhyloP100		-1.1
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: rs547561; hg19: chr11-102643894;