Variant rs2072788 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001393530.1(MATN4):c.490C>T(p.Arg164Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,346,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R164S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38482526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN4	NM_001393530.1 linkuse as main transcript	c.490C>T	p.Arg164Cys	missense_variant	3/10	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.490C>T	p.Arg164Cys	missense_variant	3/10	1	NM_001393530.1	ENSP00000361842.1	O95460-2
MATN4	ENST00000372754.5 linkuse as main transcript	c.490C>T	p.Arg164Cys	missense_variant	2/10	5		ENSP00000361840.1	O95460-1
MATN4	ENST00000360607.10 linkuse as main transcript	c.490C>T	p.Arg164Cys	missense_variant	3/9	1		ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000670

AC:

AN:

149258

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000768

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.43e-7

AC:

AN:

1346138

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

657846

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:

0.0000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000864

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.93

.;D;D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

1.5

L;L;L;.;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Uncertain

0.50

Sift

Uncertain

0.012

.;.;D;D;.

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.92

P;.;D;D;P

Vest4

0.38

MutPred

0.62

Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);

MVP

0.91

MPC

1.3

ClinPred

0.83

GERP RS

3.8

Varity_R

0.81

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over