Genetic Variant MATN4:p.Thr534Ile (chr20-45293994-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393530.1(MATN4):c.1601C>T(p.Thr534Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T534R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.64

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20015007).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393530.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MATN4	NM_001393530.1	MANE Select	c.1601C>T	p.Thr534Ile	missense	Exon 9 of 10	NP_001380459.1	O95460-2
MATN4	NM_003833.5		c.1601C>T	p.Thr534Ile	missense	Exon 10 of 11	NP_003824.2
MATN4	NM_001393531.1		c.1601C>T	p.Thr534Ile	missense	Exon 9 of 9	NP_001380460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MATN4	ENST00000372756.6	TSL:1 MANE Select	c.1601C>T	p.Thr534Ile	missense	Exon 9 of 10	ENSP00000361842.1	O95460-2
MATN4	ENST00000372754.5	TSL:5	c.1724C>T	p.Thr575Ile	missense	Exon 9 of 10	ENSP00000361840.1	O95460-1
MATN4	ENST00000360607.10	TSL:1	c.1478C>T	p.Thr493Ile	missense	Exon 8 of 9	ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450390

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111718

Other (OTH)

AF:

0.00

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.013

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.027

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.8

PhyloP100

3.6

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.0

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.20

Polyphen

0.015

Vest4

0.22

MutPred

0.40

Loss of disorder (P = 0.0349)

MVP

0.80

MPC

0.49

ClinPred

0.77

GERP RS

4.8

Varity_R

0.45

gMVP

0.60

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over