11-102772873-G-T

Variant names:

• chr11-102772873-G-T
• rs147267769
• NM_002425.3:c.1200C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_002425.3(MMP10):​c.1200C>A​(p.Tyr400*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,613,068 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (12 hom.)
• Consequence: MMP10 NM_002425.3 stop_gained
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300
• Publications: 12 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.

• BP6: Variant 11-102772873-G-T is Benign according to our data. Variant chr11-102772873-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.1200C>A	p.Tyr400*	stop_gained	Exon 8 of 10	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.1200C>A	p.Tyr400*	stop_gained	Exon 8 of 10	1	NM_002425.3	ENSP00000279441.4
WTAPP1	ENST00000371455.7	n.324+21447G>T		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1	n.188+21447G>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 373 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00233 AC: 584 AN: 250532 AF XY: 0.00228

Gnomad AFR exome AF: 0.000801

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000972

Gnomad NFE exome AF: 0.00445

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00388 AC: 5673 AN: 1460786 Hom.: 12 Cov.: 30 AF XY: 0.00377 AC XY: 2737 AN XY: 726630

African (AFR) AF: 0.000569 AC: 19 AN: 33420

American (AMR) AF: 0.000807 AC: 36 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.000244 AC: 21 AN: 85934

European-Finnish (FIN) AF: 0.000843 AC: 45 AN: 53396

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5764

European-Non Finnish (NFE) AF: 0.00479 AC: 5325 AN: 1111570

Other (OTH) AF: 0.00335 AC: 202 AN: 60362

GnomAD4 genome AF: 0.00244 AC: 372 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74470

African (AFR) AF: 0.000698 AC: 29 AN: 41552

American (AMR) AF: 0.00124 AC: 19 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00463 AC: 315 AN: 68014

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00359 Hom.: 4

Bravo AF: 0.00245

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00245 AC: 297

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00486

EpiControl AF: 0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		0.030
Vest4		0.71
GERP RS		0.46
Mutation Taster		=172/28	disease causing (fs/PTC)

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: rs147267769; hg19: chr11-102643604;