rs569444

Variant names:

• chr11-102836574-G-A
• rs569444
• NM_002422.5:c.1334-348C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102836574-G-A
• chr11-102836574-G-T

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.1334-348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 485,038 control chromosomes in the GnomAD database, including 4,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3211 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.607
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-102836574-G-A is Benign according to our data. Variant chr11-102836574-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263820.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.1334-348C>T		intron_variant	Intron 9 of 9	ENST00000299855.10	NP_002413.1
WTAPP1	NR_038390.1	n.2450G>A		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.1334-348C>T		intron_variant	Intron 9 of 9	1	NM_002422.5	ENSP00000299855.5
WTAPP1	ENST00000525739.6	n.2450G>A		non_coding_transcript_exon_variant	Exon 8 of 8	2
MMP3	ENST00000434103.1	c.263-46C>T		intron_variant	Intron 2 of 2	3		ENSP00000398346.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15855 AN: 151982 Hom.: 1229 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.120 AC: 18070 AN: 150284 AF XY: 0.119

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.0748

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0712

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.127 AC: 42184 AN: 332938 Hom.: 3211 Cov.: 0 AF XY: 0.124 AC XY: 23162 AN XY: 187376

African (AFR) AF: 0.0235 AC: 218 AN: 9260

American (AMR) AF: 0.0746 AC: 2055 AN: 27546

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 1521 AN: 11406

East Asian (EAS) AF: 0.0838 AC: 856 AN: 10216

South Asian (SAS) AF: 0.0849 AC: 5072 AN: 59730

European-Finnish (FIN) AF: 0.247 AC: 6861 AN: 27826

Middle Eastern (MID) AF: 0.139 AC: 397 AN: 2860

European-Non Finnish (NFE) AF: 0.138 AC: 23297 AN: 168652

Other (OTH) AF: 0.123 AC: 1907 AN: 15442

GnomAD4 genome AF: 0.104 AC: 15855 AN: 152100 Hom.: 1229 Cov.: 32 AF XY: 0.108 AC XY: 8057 AN XY: 74322

African (AFR) AF: 0.0247 AC: 1026 AN: 41510

American (AMR) AF: 0.0838 AC: 1282 AN: 15290

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

East Asian (EAS) AF: 0.0719 AC: 372 AN: 5174

South Asian (SAS) AF: 0.0786 AC: 378 AN: 4808

European-Finnish (FIN) AF: 0.278 AC: 2933 AN: 10544

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

European-Non Finnish (NFE) AF: 0.133 AC: 9069 AN: 67986

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.122 Hom.: 279

Bravo AF: 0.0873

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.72
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs569444; hg19: chr11-102707305; COSMIC: COSV55406321; COSMIC: COSV55406321;