dbSNP rs111737060: MATN4:p.Leu561Met (chr20-45293914-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001393530.1(MATN4):c.1681C>A(p.Leu561Met) variant causes a missense change. The variant allele was found at a frequency of 0.000314 in 1,603,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.94

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004840493).

BP6

Variant 20-45293914-G-T is Benign according to our data. Variant chr20-45293914-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3038510.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1681C>A	p.Leu561Met	missense	Exon 9 of 10	NP_001380459.1	O95460-2
MATN4	NM_003833.5		c.1681C>A	p.Leu561Met	missense	Exon 10 of 11	NP_003824.2
MATN4	NM_001393531.1		c.1681C>A	p.Leu561Met	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.1681C>A	p.Leu561Met	missense	Exon 9 of 10	ENSP00000361842.1	O95460-2
MATN4	ENST00000372754.5	TSL:5	c.1804C>A	p.Leu602Met	missense	Exon 9 of 10	ENSP00000361840.1	O95460-1
MATN4	ENST00000360607.10	TSL:1	c.1558C>A	p.Leu520Met	missense	Exon 8 of 9	ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00552

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000420

AC:

101

AN:

240614

AF XY:

0.000244

show subpopulations

Gnomad AFR exome

AF:

0.00474

Gnomad AMR exome

AF:

0.000364

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000983

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.000177

AC:

257

AN:

1450808

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

722216

show subpopulations

African (AFR)

AF:

0.00502

AC:

166

AN:

33056

American (AMR)

AF:

0.000390

AC:

AN:

43608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25996

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39418

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46422

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1110656

Other (OTH)

AF:

0.000515

AC:

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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

AF:

0.00161

AC:

246

AN:

152348

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00555

AC:

231

AN:

41592

American (AMR)

AF:

0.000523

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68032

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000531

Hom.:

Bravo

AF:

0.00178

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000469

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000238

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MATN4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0038

Eigen

Benign

0.083

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.34

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

3.9

PrimateAI

Benign

0.27

PROVEAN

Benign

0.80

REVEL

Benign

0.12

Sift

Benign

0.077

Sift4G

Uncertain

0.054

Polyphen

0.47

Vest4

0.17

MVP

0.19

MPC

0.79

ClinPred

0.037

GERP RS

4.7

Varity_R

0.27

gMVP

0.23

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over