NM_001393530.1:c.1603G>C

Variant names:

• chr20-45293992-C-G
• rs769837832
• NM_001393530.1:c.1603G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393530.1(MATN4):​c.1603G>C​(p.Glu535Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37567896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN4	NM_001393530.1	c.1603G>C	p.Glu535Gln	missense_variant	Exon 9 of 10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6	c.1603G>C	p.Glu535Gln	missense_variant	Exon 9 of 10	1	NM_001393530.1	ENSP00000361842.1
MATN4	ENST00000372754.5	c.1726G>C	p.Glu576Gln	missense_variant	Exon 9 of 10	5		ENSP00000361840.1
MATN4	ENST00000360607.10	c.1480G>C	p.Glu494Gln	missense_variant	Exon 8 of 9	1		ENSP00000353819.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450424 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	.;T;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	.;T;T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Uncertain	0.012	D
MutationAssessor	Uncertain	2.5	.;M;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.10	.;.;T;T;.
Sift4G	Benign	0.076	T;T;T;T;T
Polyphen		1.0	D;.;D;D;D
Vest4		0.49
MutPred		0.52		.;.;.;Loss of disorder (P = 0.0909);.;
MVP		0.88
MPC		1.2
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.51
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs769837832; hg19: chr20-43922632;