chr11-102776579-T-G

Variant names:

• chr11-102776579-T-G
• rs470154
• NM_002425.3:c.787+33A>C

Variant summary

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

The NM_002425.3(MMP10):​c.787+33A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 1,599,310 control chromosomes in the GnomAD database, including 691,832 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 (67718 hom., cov: 32)
  • Exomes 𝑓: 0.93 (624114 hom.)
• Consequence: MMP10 NM_002425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002425.3. 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
	MMP10	NM_002425.3	MANE Select	c.787+33A>C		intron	N/A	NP_002416.1	P09238

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP10	ENST00000279441.9	TSL:1 MANE Select	c.787+33A>C		intron	N/A	ENSP00000279441.4	P09238
	WTAPP1	ENST00000371455.7	TSL:4	n.325-21445T>G		intron	N/A
	WTAPP1	ENST00000817290.1		n.189-21445T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143361 AN: 152148 Hom.: 67656 Cov.: 32

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.895

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

GnomAD2 exomes AF: 0.919 AC: 221528 AN: 240934 AF XY: 0.921

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.845

Gnomad ASJ exome AF: 0.937

Gnomad EAS exome AF: 0.886

Gnomad FIN exome AF: 0.919

Gnomad NFE exome AF: 0.940

Gnomad OTH exome AF: 0.929

GnomAD4 exome AF: 0.928 AC: 1343426 AN: 1447044 Hom.: 624114 Cov.: 37 AF XY: 0.928 AC XY: 667064 AN XY: 719146

African (AFR) AF: 0.990 AC: 32268 AN: 32606

American (AMR) AF: 0.853 AC: 35064 AN: 41124

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 23884 AN: 25526

East Asian (EAS) AF: 0.884 AC: 35005 AN: 39592

South Asian (SAS) AF: 0.897 AC: 75407 AN: 84074

European-Finnish (FIN) AF: 0.924 AC: 49130 AN: 53164

Middle Eastern (MID) AF: 0.931 AC: 5244 AN: 5632

European-Non Finnish (NFE) AF: 0.933 AC: 1031907 AN: 1105580

Other (OTH) AF: 0.929 AC: 55517 AN: 59746

GnomAD4 genome AF: 0.942 AC: 143482 AN: 152266 Hom.: 67718 Cov.: 32 AF XY: 0.939 AC XY: 69936 AN XY: 74442

African (AFR) AF: 0.986 AC: 40990 AN: 41572

American (AMR) AF: 0.899 AC: 13744 AN: 15296

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

East Asian (EAS) AF: 0.895 AC: 4630 AN: 5174

South Asian (SAS) AF: 0.902 AC: 4344 AN: 4818

European-Finnish (FIN) AF: 0.914 AC: 9685 AN: 10594

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

European-Non Finnish (NFE) AF: 0.937 AC: 63767 AN: 68020

Other (OTH) AF: 0.934 AC: 1976 AN: 2116

Alfa AF: 0.938 Hom.: 19946

Bravo AF: 0.941

Asia WGS AF: 0.908 AC: 3161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.39
PhyloP100		-0.079
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: rs470154; hg19: chr11-102647310;