rs7922546

Variant names:

• chr10-125772184-G-A
• rs7922546
• NM_147191.1:c.979+34C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147191.1(MMP21):​c.979+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,611,146 control chromosomes in the GnomAD database, including 94,374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7536 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86838 hom.)
• Consequence: MMP21 NM_147191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 13 publications found

Genes affected

MMP21 (HGNC:14357): (matrix metallopeptidase 21) This gene encodes a member of the matrix metalloproteinase family. Proteins in this family are involved in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, and disease processes, such as asthma and tumor metastasis. The encoded protein may play an important role in embryogenesis, particularly in neuronal cells, as well as in lymphocyte development and survival. [provided by RefSeq, May 2013]

MMP21 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 7, autosomal

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147191.1. 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
	MMP21	NM_147191.1	MANE Select	c.979+34C>T		intron	N/A	NP_671724.1	Q8N119

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP21	ENST00000368808.3	TSL:1 MANE Select	c.979+34C>T		intron	N/A	ENSP00000357798.3	Q8N119
	MMP21	ENST00000651977.2		c.698-1593C>T		intron	N/A	ENSP00000499059.2
	MMP21	ENST00000651834.1		n.180+427C>T		intron	N/A	ENSP00000498515.1	A0A494C0E5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46351 AN: 151924 Hom.: 7545 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.335 AC: 83753 AN: 250090 AF XY: 0.340

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.341 AC: 498078 AN: 1459104 Hom.: 86838 Cov.: 32 AF XY: 0.341 AC XY: 247674 AN XY: 725926

African (AFR) AF: 0.208 AC: 6947 AN: 33448

American (AMR) AF: 0.346 AC: 15450 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9403 AN: 26000

East Asian (EAS) AF: 0.146 AC: 5797 AN: 39686

South Asian (SAS) AF: 0.337 AC: 29012 AN: 86052

European-Finnish (FIN) AF: 0.431 AC: 23000 AN: 53312

Middle Eastern (MID) AF: 0.353 AC: 2024 AN: 5728

European-Non Finnish (NFE) AF: 0.348 AC: 386432 AN: 1109896

Other (OTH) AF: 0.332 AC: 20013 AN: 60304

GnomAD4 genome AF: 0.305 AC: 46358 AN: 152042 Hom.: 7536 Cov.: 32 AF XY: 0.310 AC XY: 23050 AN XY: 74300

African (AFR) AF: 0.208 AC: 8646 AN: 41486

American (AMR) AF: 0.309 AC: 4724 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1237 AN: 3468

East Asian (EAS) AF: 0.164 AC: 846 AN: 5154

South Asian (SAS) AF: 0.331 AC: 1593 AN: 4816

European-Finnish (FIN) AF: 0.428 AC: 4514 AN: 10558

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23801 AN: 67972

Other (OTH) AF: 0.302 AC: 637 AN: 2108

Alfa AF: 0.336 Hom.: 15571

Bravo AF: 0.291

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.34
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: rs7922546; hg19: chr10-127460753; COSMIC: COSV64289001;