20-45293788-G-T

Variant names:

• chr20-45293788-G-T
• rs2233106
• NM_001393530.1:c.1725C>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.1725C>A​(p.Asn575Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,610,250 control chromosomes in the GnomAD database, including 368 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 0.026 (174 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (194 hom.)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.314
• Publications: 6 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=0.0015662313).
• BP6: Variant 20-45293788-G-T is Benign according to our data. Variant chr20-45293788-G-T is described in ClinVar as Benign. ClinVar VariationId is 785656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393530.1. 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
	MATN4	NM_001393530.1	MANE Select	c.1725C>A	p.Asn575Lys	missense	Exon 10 of 10	NP_001380459.1	O95460-2
	MATN4	NM_003833.5		c.1725C>A	p.Asn575Lys	missense	Exon 11 of 11	NP_003824.2
	MATN4	NM_030590.4		c.1602C>A	p.Asn534Lys	missense	Exon 9 of 9	NP_085080.1	O95460-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN4	ENST00000372756.6	TSL:1 MANE Select	c.1725C>A	p.Asn575Lys	missense	Exon 10 of 10	ENSP00000361842.1	O95460-2
	MATN4	ENST00000372754.5	TSL:5	c.1848C>A	p.Asn616Lys	missense	Exon 10 of 10	ENSP00000361840.1	O95460-1
	MATN4	ENST00000360607.10	TSL:1	c.1602C>A	p.Asn534Lys	missense	Exon 9 of 9	ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4005 AN: 152226 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.00688 AC: 1697 AN: 246672 AF XY: 0.00529

Gnomad AFR exome AF: 0.0926

Gnomad AMR exome AF: 0.00476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000330

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00275 AC: 4003 AN: 1457906 Hom.: 194 Cov.: 32 AF XY: 0.00237 AC XY: 1719 AN XY: 725448

African (AFR) AF: 0.0983 AC: 3286 AN: 33442

American (AMR) AF: 0.00528 AC: 236 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50454

Middle Eastern (MID) AF: 0.00264 AC: 14 AN: 5296

European-Non Finnish (NFE) AF: 0.0000998 AC: 111 AN: 1111802

Other (OTH) AF: 0.00568 AC: 342 AN: 60258

GnomAD4 genome AF: 0.0263 AC: 4009 AN: 152344 Hom.: 174 Cov.: 32 AF XY: 0.0252 AC XY: 1879 AN XY: 74498

African (AFR) AF: 0.0909 AC: 3780 AN: 41572

American (AMR) AF: 0.0110 AC: 169 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68034

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.00689 Hom.: 103

Bravo AF: 0.0308

ESP6500AA AF: 0.0858 AC: 378

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00826 AC: 1003

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MATN4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.31
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.046
Sift	Benign	0.15	T
Sift4G	Benign	0.27	T
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.58		Gain of ubiquitination at N493 (P = 0.0069)
MVP		0.43
MPC		0.51
ClinPred		0.018	T
GERP RS		-3.2
Varity_R		0.38
gMVP		0.39
Mutation Taster		=97/3	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: rs2233106; hg19: chr20-43922428;