rs147573175

Variant names:

• chr11-102713423-G-A
• rs147573175
• NM_002424.3:c.1329C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102713423-G-A
• chr11-102713423-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002424.3(MMP8):​c.1329C>T​(p.Tyr443Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,613,244 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: MMP8 NM_002424.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.196
• Publications: 2 publications found

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-102713423-G-A is Benign according to our data. Variant chr11-102713423-G-A is described in ClinVar as Benign. ClinVar VariationId is 779312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. 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
	MMP8	NM_002424.3	MANE Select	c.1329C>T	p.Tyr443Tyr	synonymous	Exon 10 of 10	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.1260C>T	p.Tyr420Tyr	synonymous	Exon 11 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.1260C>T	p.Tyr420Tyr	synonymous	Exon 11 of 11	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.1329C>T	p.Tyr443Tyr	synonymous	Exon 10 of 10	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.*68C>T		3_prime_UTR	Exon 9 of 9	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*1306C>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes AF: 0.00373 AC: 567 AN: 152100 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000830 AC: 208 AN: 250728 AF XY: 0.000546

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000342 AC: 500 AN: 1461026 Hom.: 1 Cov.: 31 AF XY: 0.000305 AC XY: 222 AN XY: 726850

African (AFR) AF: 0.0121 AC: 404 AN: 33412

American (AMR) AF: 0.000358 AC: 16 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86238

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53398

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111404

Other (OTH) AF: 0.000945 AC: 57 AN: 60348

GnomAD4 genome AF: 0.00376 AC: 572 AN: 152218 Hom.: 3 Cov.: 33 AF XY: 0.00363 AC XY: 270 AN XY: 74422

African (AFR) AF: 0.0129 AC: 535 AN: 41544

American (AMR) AF: 0.00190 AC: 29 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00132 Hom.: 3

Bravo AF: 0.00420

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.30
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism

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: rs147573175; hg19: chr11-102584154; COSMIC: COSV99368961;