20-45304381-G-T

Position:

• chr20-45304381-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001393530.1(MATN4):​c.490C>A​(p.Arg164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,497,804 control chromosomes in the GnomAD database, including 72,291 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.28 (6881 hom., cov: 33)
  • Exomes 𝑓: 0.30 (65410 hom.)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.14

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.0037684E-6).
• BP6: Variant 20-45304381-G-T is Benign according to our data. Variant chr20-45304381-G-T is described in ClinVar as [Benign]. Clinvar id is 1338928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN4	NM_001393530.1	c.490C>A	p.Arg164Ser	missense_variant	3/10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6	c.490C>A	p.Arg164Ser	missense_variant	3/10	1	NM_001393530.1	ENSP00000361842.1
MATN4	ENST00000372754.5	c.490C>A	p.Arg164Ser	missense_variant	2/10	5		ENSP00000361840.1
MATN4	ENST00000360607.10	c.490C>A	p.Arg164Ser	missense_variant	3/9	1		ENSP00000353819.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42538 AN: 151970 Hom.: 6874 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.350 AC: 52282 AN: 149258 Hom.: 10694 AF XY: 0.345 AC XY: 28161 AN XY: 81732

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.767

Gnomad SAS exome AF: 0.443

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.299 AC: 401842 AN: 1345716 Hom.: 65410 Cov.: 34 AF XY: 0.301 AC XY: 197899 AN XY: 657590

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.280 AC: 42567 AN: 152088 Hom.: 6881 Cov.: 33 AF XY: 0.285 AC XY: 21180 AN XY: 74358

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.288

Alfa AF: 0.301 Hom.: 11539

Bravo AF: 0.284

TwinsUK AF: 0.276 AC: 1025

ALSPAC AF: 0.263 AC: 1014

ESP6500AA AF: 0.194 AC: 831

ESP6500EA AF: 0.268 AC: 2226

ExAC AF: 0.330 AC: 38194

Asia WGS AF: 0.561 AC: 1948 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Jan 27, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.011	.;T;.;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.50	.;T;T;T;T
MetaRNN	Benign	0.0000030	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.3	N;N;N;.;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.6	N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	1.0	.;.;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0010	B;.;B;B;B
Vest4		0.16
MPC		0.50
ClinPred		0.0079	T
GERP RS		3.8
Varity_R		0.24
gMVP		0.72

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: rs2072788; hg19: chr20-43933021; COSMIC: COSV59212722; COSMIC: COSV59212722;