Genetic Variant MATN1:p.Cys12Arg (chr1-30723518-A-G) – 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_002379.3(MATN1):c.34T>C(p.Cys12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,383,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

MATN1
NM_002379.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.360

Publications

0 publications found

Variant links:

Genes affected

MATN1 (HGNC:6907): (matrilin 1) This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. Mutations of this gene have been associated with variety of inherited chondrodysplasias. [provided by RefSeq, Jul 2008]

MATN1 links:

MATN1-AS1 (HGNC:40364): (MATN1 antisense RNA 1)

MATN1-AS1 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=0.21139288).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002379.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN1	NM_002379.3	MANE Select	c.34T>C	p.Cys12Arg	missense	Exon 1 of 8	NP_002370.1	P21941
	MATN1-AS1	NR_034182.1		n.1229+1796A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MATN1	ENST00000373765.5	TSL:1 MANE Select	c.34T>C	p.Cys12Arg	missense	Exon 1 of 8	ENSP00000362870.4	P21941
MATN1-AS1	ENST00000454613.2	TSL:1	n.1232+1796A>G		intron	N/A
MATN1-AS1	ENST00000414532.6	TSL:2	n.3106+1796A>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000282

AC:

AN:

141994

AF XY:

0.0000398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000419

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000434

AC:

AN:

1383920

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30604

American (AMR)

AF:

0.00

AC:

AN:

33588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24798

East Asian (EAS)

AF:

0.000174

AC:

AN:

34406

South Asian (SAS)

AF:

0.00

AC:

AN:

76666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5598

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072486

Other (OTH)

AF:

0.00

AC:

AN:

57448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.23

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.37

M_CAP

Benign

0.023

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.36

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.22

Sift

Uncertain

0.0070

Sift4G

Benign

0.094

Polyphen

0.12

Vest4

0.44

MutPred

0.65

Gain of MoRF binding (P = 0.001)

MVP

0.26

MPC

0.43

ClinPred

0.035

GERP RS

-3.0

PromoterAI

0.024

Neutral

(source)

Varity_R

0.27

gMVP

0.51

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over