rs646910

Variant names:

• chr11-102838791-T-A
• rs646910
• NM_002422.5:c.1070-81A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102838791-T-A
• chr11-102838791-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002422.5(MMP3):​c.1070-81A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,440,300 control chromosomes in the GnomAD database, including 12,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1259 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11057 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.145
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-102838791-T-A is Benign according to our data. Variant chr11-102838791-T-A is described in ClinVar as Benign. ClinVar VariationId is 1274196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.1070-81A>T		intron	N/A	NP_002413.1	P08254

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	ENST00000299855.10	TSL:1 MANE Select	c.1070-81A>T		intron	N/A	ENSP00000299855.5	P08254
	MMP3	ENST00000434103.1	TSL:3	c.-83A>T		upstream_gene	N/A	ENSP00000398346.1	H7C139

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16432 AN: 152118 Hom.: 1259 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.124 AC: 160357 AN: 1288064 Hom.: 11057 AF XY: 0.124 AC XY: 79256 AN XY: 640600

African (AFR) AF: 0.0285 AC: 783 AN: 27504

American (AMR) AF: 0.0771 AC: 1927 AN: 24994

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3109 AN: 23302

East Asian (EAS) AF: 0.0982 AC: 3492 AN: 35574

South Asian (SAS) AF: 0.0824 AC: 5902 AN: 71656

European-Finnish (FIN) AF: 0.246 AC: 11518 AN: 46816

Middle Eastern (MID) AF: 0.134 AC: 675 AN: 5022

European-Non Finnish (NFE) AF: 0.127 AC: 126668 AN: 999082

Other (OTH) AF: 0.116 AC: 6283 AN: 54114

GnomAD4 genome AF: 0.108 AC: 16433 AN: 152236 Hom.: 1259 Cov.: 33 AF XY: 0.112 AC XY: 8335 AN XY: 74420

African (AFR) AF: 0.0368 AC: 1530 AN: 41560

American (AMR) AF: 0.0858 AC: 1313 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3472

East Asian (EAS) AF: 0.0723 AC: 375 AN: 5186

South Asian (SAS) AF: 0.0791 AC: 382 AN: 4828

European-Finnish (FIN) AF: 0.279 AC: 2953 AN: 10570

Middle Eastern (MID) AF: 0.131 AC: 38 AN: 290

European-Non Finnish (NFE) AF: 0.133 AC: 9078 AN: 68008

Other (OTH) AF: 0.107 AC: 226 AN: 2114

Alfa AF: 0.126 Hom.: 184

Bravo AF: 0.0911

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.14
PromoterAI		-0.0091	Neutral
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: rs646910; hg19: chr11-102709522;