20-45298307-T-C

Variant names:

• chr20-45298307-T-C
• rs1985992665
• NM_001393530.1:c.1289A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001393530.1(MATN4):​c.1289A>G​(p.His430Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

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.1289A>G	p.His430Arg	missense	Exon 7 of 10	NP_001380459.1	O95460-2
	MATN4	NM_003833.5		c.1289A>G	p.His430Arg	missense	Exon 8 of 11	NP_003824.2
	MATN4	NM_001393531.1		c.1289A>G	p.His430Arg	missense	Exon 7 of 9	NP_001380460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN4	ENST00000372756.6	TSL:1 MANE Select	c.1289A>G	p.His430Arg	missense	Exon 7 of 10	ENSP00000361842.1	O95460-2
	MATN4	ENST00000372754.5	TSL:5	c.1412A>G	p.His471Arg	missense	Exon 7 of 10	ENSP00000361840.1	O95460-1
	MATN4	ENST00000360607.10	TSL:1	c.1166A>G	p.His389Arg	missense	Exon 6 of 9	ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Benign	2.0	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.1	D
REVEL	Pathogenic	0.81
Sift	Benign	0.076	T
Sift4G	Benign	0.087	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.64		Gain of MoRF binding (P = 0.0117)
MVP		0.95
MPC		1.4
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.92
gMVP		0.93
Mutation Taster		=6/94	disease causing

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: rs1985992665; hg19: chr20-43926947;