1-30715172-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002379.3(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 NM_002379.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN1	NM_002379.3	c.1345A>C	p.Lys449Gln	missense_variant	6/8	ENST00000373765.5

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 1061 AN: 152198 Hom.: 11 Cov.: 33

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.: 4 AF XY: 0.00213 AC XY: 290 AN XY: 135886

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.: 15 Cov.: 31 AF XY: 0.00110 AC XY: 799 AN XY: 727242

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.: 12 Cov.: 33 AF XY: 0.00694 AC XY: 517 AN XY: 74488

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.: 3

Bravo AF: 0.00842

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0252 AC: 111

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00268 AC: 326

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	18
Dann	Benign	0.85
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.21	N
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.10
Sift	Benign	0.47	T
Sift4G	Benign	0.59	T
Polyphen		0.29	B
Vest4		0.19
MVP		0.53
MPC		0.37
ClinPred		0.0057	T
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

Other links and lift over

dbSNP: rs56851503; hg19: chr1-31188019;