Variant 1-30715172-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000373765.5(MATN1):c.1345A>C(p.Lys449Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,614,190 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 15 hom. )

Consequence

MATN1
ENST00000373765.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037178397).

BP6

Variant 1-30715172-T-G is Benign according to our data. Variant chr1-30715172-T-G is described in ClinVar as [Benign]. Clinvar id is 791787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00704 (1072/152316) while in subpopulation AFR AF= 0.0232 (965/41560). AF 95% confidence interval is 0.022. There are 12 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN1	NM_002379.3 linkuse as main transcript	c.1345A>C	p.Lys449Gln	missense_variant	6/8	ENST00000373765.5	NP_002370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN1	ENST00000373765.5 linkuse as main transcript	c.1345A>C	p.Lys449Gln	missense_variant	6/8	1	NM_002379.3	ENSP00000362870	P1
MATN1	ENST00000494561.1 linkuse as main transcript	n.365A>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00697

AC:

1061

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00256

AC:

644

AN:

251420

Hom.:

AF XY:

0.00213

AC XY:

290

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00120

AC:

1759

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

799

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00807

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000306

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00704

AC:

1072

AN:

152316

Hom.:

Cov.:

AF XY:

0.00694

AC XY:

517

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00842

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0252

AC:

111

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00268

AC:

326

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.089

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.21

MutationTaster

Benign

0.99

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.37

REVEL

Benign

0.10

Sift

Benign

0.47

Sift4G

Benign

0.59

Polyphen

0.29

Vest4

0.19

MVP

0.53

MPC

0.37

ClinPred

0.0057

GERP RS

2.5

Varity_R

0.061

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over