chr20-45297977-G-A

Position:

• chr20-45297977-G-A

Variant summary

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

The NM_001393530.1(MATN4):​c.1520C>T​(p.Ala507Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.65

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/exons	MANE	UniProt
MATN4	NM_001393530.1	c.1520C>T	p.Ala507Val	missense_variant	8/10	ENST00000372756.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN4	ENST00000372756.6	c.1520C>T	p.Ala507Val	missense_variant	8/10	1	NM_001393530.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461850 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727236

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.1520C>T (p.A507V) alteration is located in exon 8 (coding exon 7) of the MATN4 gene. This alteration results from a C to T substitution at nucleotide position 1520, causing the alanine (A) at amino acid position 507 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.45
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0074
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	0.99	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N;N;N;N;N
REVEL	Uncertain	0.32
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.10	B;.;P;B;B
Vest4		0.32
MutPred		0.62		.;.;.;Loss of disorder (P = 0.1412);.;
MVP		0.88
MPC		0.53
ClinPred		0.62	D
GERP RS		5.6
Varity_R		0.40
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43926617; COSMIC: COSV61352966;