rs547561

Positions:

• chr11-102773163-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MMP10	NM_002425.3	c.1067-157G>A		intron_variant		ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.1067-157G>A		intron_variant		1	NM_002425.3	ENSP00000279441.4
WTAPP1	ENST00000371455.7	n.324+21737C>T		intron_variant		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

Gnomad4 AFR AF: 0.986

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.934

Alfa AF: 0.937 Hom.: 85864

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

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: rs547561; hg19: chr11-102643894;