rs372872290

Variant names:

• chr20-45298344-T-C
• NM_001393530.1:c.1252A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-45298344-T-C
• chr20-45298344-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001393530.1(MATN4):​c.1252A>G​(p.Met418Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,124 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08

Genes affected

MATN4 (HGNC:6910): (matrilin 4) This gene encodes a member of von Willebrand factor A domain-containing protein family. The proteins of this family are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This family member is thought to be play a role in reorganizing and regenerating the corneal matrix in granular and lattice type I dystrophies. It may also be involved in wound healing in the dentin-pulp complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN4	NM_001393530.1	c.1252A>G	p.Met418Val	missense_variant	Exon 7 of 10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6	c.1252A>G	p.Met418Val	missense_variant	Exon 7 of 10	1	NM_001393530.1	ENSP00000361842.1
MATN4	ENST00000372754.5	c.1375A>G	p.Met459Val	missense_variant	Exon 7 of 10	5		ENSP00000361840.1
MATN4	ENST00000360607.10	c.1129A>G	p.Met377Val	missense_variant	Exon 6 of 9	1		ENSP00000353819.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461124 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	.;T;.;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	.;D;D;D;D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.4	.;M;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0020	.;.;D;D;.
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		0.99	D;.;P;D;D
Vest4		0.52
MutPred		0.55		.;.;.;Loss of phosphorylation at Y335 (P = 0.1287);.;
MVP		0.92
MPC		1.3
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.91
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43926984;