chr11-102836635-A-T

Variant names:

• chr11-102836635-A-T
• rs563096
• NM_002422.5:c.1334-409T>A

Variant summary

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

The NM_002422.5(MMP3):​c.1334-409T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 460,442 control chromosomes in the GnomAD database, including 4,189 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 0.10 (1233 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2956 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 9 publications found

Genes affected

MMP3 (HGNC:7173): (matrix metallopeptidase 3) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

WTAPP1 (HGNC:):

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002422.5. 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
	MMP3	NM_002422.5	MANE Select	c.1334-409T>A		intron	N/A	NP_002413.1	P08254
	WTAPP1	NR_038390.1		n.2511A>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	ENST00000299855.10	TSL:1 MANE Select	c.1334-409T>A		intron	N/A	ENSP00000299855.5	P08254
	MMP3	ENST00000434103.1	TSL:3	c.263-107T>A		intron	N/A	ENSP00000398346.1	H7C139
	WTAPP1	ENST00000525739.6	TSL:2	n.2511A>T		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15857 AN: 151922 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.126 AC: 38926 AN: 308402 Hom.: 2956 Cov.: 0 AF XY: 0.123 AC XY: 21283 AN XY: 173346

African (AFR) AF: 0.0238 AC: 200 AN: 8418

American (AMR) AF: 0.0738 AC: 1938 AN: 26244

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 1325 AN: 10106

East Asian (EAS) AF: 0.0803 AC: 735 AN: 9150

South Asian (SAS) AF: 0.0849 AC: 4866 AN: 57330

European-Finnish (FIN) AF: 0.247 AC: 6648 AN: 26876

Middle Eastern (MID) AF: 0.138 AC: 373 AN: 2702

European-Non Finnish (NFE) AF: 0.137 AC: 21092 AN: 153510

Other (OTH) AF: 0.124 AC: 1749 AN: 14066

GnomAD4 genome AF: 0.104 AC: 15857 AN: 152040 Hom.: 1233 Cov.: 32 AF XY: 0.108 AC XY: 8059 AN XY: 74288

African (AFR) AF: 0.0246 AC: 1021 AN: 41490

American (AMR) AF: 0.0841 AC: 1284 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3466

East Asian (EAS) AF: 0.0725 AC: 375 AN: 5170

South Asian (SAS) AF: 0.0792 AC: 381 AN: 4808

European-Finnish (FIN) AF: 0.279 AC: 2936 AN: 10542

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9066 AN: 67976

Other (OTH) AF: 0.103 AC: 216 AN: 2106

Alfa AF: 0.124 Hom.: 184

Bravo AF: 0.0873

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.75
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: rs563096; hg19: chr11-102707366; COSMIC: COSV55407393; COSMIC: COSV55407393;