14-22836774-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004995.4(MMP14):c.-44G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,336,282 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (48 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (53 hom.)
• Consequence: MMP14 NM_004995.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.454

Genes affected

MMP14 (HGNC:7160): (matrix metallopeptidase 14) 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. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 14-22836774-G-C is Benign according to our data. Variant chr14-22836774-G-C is described in ClinVar as [Benign]. Clinvar id is 1273921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP14	NM_004995.4	c.-44G>C		5_prime_UTR_variant	1/10	ENST00000311852.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP14	ENST00000311852.11	c.-44G>C		5_prime_UTR_variant	1/10	1	NM_004995.4	P1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2262 AN: 152170 Hom.: 49 Cov.: 31

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00398 AC: 549 AN: 137896 Hom.: 10 AF XY: 0.00325 AC XY: 244 AN XY: 75030

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000606

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000678

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00154 AC: 1825 AN: 1183994 Hom.: 53 Cov.: 16 AF XY: 0.00138 AC XY: 810 AN XY: 585006

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.0000503

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000590

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000376

Gnomad4 OTH exome AF: 0.00382

GnomAD4 genome AF: 0.0149 AC: 2269 AN: 152288 Hom.: 48 Cov.: 31 AF XY: 0.0139 AC XY: 1035 AN XY: 74452

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00770 Hom.: 8

Bravo AF: 0.0172

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	8.6
Dann	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs17885183; hg19: chr14-23305983;