20-45304381-G-T

Variant names:

• chr20-45304381-G-T
• rs2072788
• NM_001393530.1:c.490C>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MATN4	NM_001393530.1	c.490C>A	p.Arg164Ser	missense_variant	Exon 3 of 10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6	c.490C>A	p.Arg164Ser	missense_variant	Exon 3 of 10	1	NM_001393530.1	ENSP00000361842.1
MATN4	ENST00000372754.5	c.490C>A	p.Arg164Ser	missense_variant	Exon 2 of 10	5		ENSP00000361840.1
MATN4	ENST00000360607.10	c.490C>A	p.Arg164Ser	missense_variant	Exon 3 of 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

GnomAD2 exomes AF: 0.350 AC: 52282 AN: 149258 AF XY: 0.345

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 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

African (AFR) AF: 0.189 AC: 5341 AN: 28228

American (AMR) AF: 0.403 AC: 11057 AN: 27440

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 6735 AN: 19722

East Asian (EAS) AF: 0.735 AC: 26962 AN: 36688

South Asian (SAS) AF: 0.425 AC: 29316 AN: 69020

European-Finnish (FIN) AF: 0.245 AC: 11767 AN: 48086

Middle Eastern (MID) AF: 0.319 AC: 1647 AN: 5166

European-Non Finnish (NFE) AF: 0.276 AC: 291650 AN: 1056086

Other (OTH) AF: 0.314 AC: 17367 AN: 55280

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

African (AFR) AF: 0.198 AC: 8219 AN: 41518

American (AMR) AF: 0.325 AC: 4972 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3826 AN: 5138

South Asian (SAS) AF: 0.429 AC: 2068 AN: 4826

European-Finnish (FIN) AF: 0.252 AC: 2666 AN: 10594

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18771 AN: 67932

Other (OTH) AF: 0.288 AC: 608 AN: 2114

Alfa AF: 0.297 Hom.: 21028

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 27, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.0	.;T;.;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.0	.;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
PhyloP100		2.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.6	N;N;N;N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	.;.;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T
Vest4		0.16
ClinPred		0.0079	T
GERP RS		3.8
Varity_R		0.24
gMVP		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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