Variant chr20-45297977-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000372756.6(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
ENST00000372756.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.65

Variant links:

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]

MATN4 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
MATN4	NM_001393530.1 linkuse as main transcript	c.1520C>T	p.Ala507Val	missense_variant	8/10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MATN4	ENST00000372756.6 linkuse as main transcript	c.1520C>T	p.Ala507Val	missense_variant	8/10	1	NM_001393530.1	ENSP00000361842.1	O95460-2
MATN4	ENST00000372754.5 linkuse as main transcript	c.1643C>T	p.Ala548Val	missense_variant	8/10	5		ENSP00000361840.1	O95460-1
MATN4	ENST00000360607.10 linkuse as main transcript	c.1397C>T	p.Ala466Val	missense_variant	7/9	1		ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727236

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.045

.;T;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0074

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.46

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.25

.;N;.;.;.

MutationTaster

Benign

0.99

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

1.0

.;.;T;T;.

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over