Genetic Variant NM_002379.3:c.1481C>G (chr1-30713592-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002379.3(MATN1):c.1481C>G(p.Thr494Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MATN1
NM_002379.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.78

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058555663).

BP6

Variant 1-30713592-G-C is Benign according to our data. Variant chr1-30713592-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2234337.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1481C>G	p.Thr494Arg	missense	Exon 8 of 8	NP_002370.1	P21941

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN1	ENST00000373765.5	TSL:1 MANE Select	c.1481C>G	p.Thr494Arg	missense	Exon 8 of 8	ENSP00000362870.4	P21941
	MATN1	ENST00000494561.1	TSL:3	n.*175C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1401624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691486

African (AFR)

AF:

0.00

AC:

AN:

31886

American (AMR)

AF:

0.00

AC:

AN:

35862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25192

East Asian (EAS)

AF:

0.00

AC:

AN:

36226

South Asian (SAS)

AF:

0.00

AC:

AN:

79370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079906

Other (OTH)

AF:

0.00

AC:

AN:

58106

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.045

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.051

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.39

M_CAP

Benign

0.0060

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.5

PhyloP100

2.8

PrimateAI

Benign

0.34

PROVEAN

Benign

1.4

REVEL

Benign

0.038

Sift

Benign

0.53

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.048

MutPred

0.42

Gain of MoRF binding (P = 3e-04)

MVP

0.36

MPC

0.28

ClinPred

0.062

GERP RS

2.3

Varity_R

0.055

gMVP

0.49

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over