20-45293994-G-C

Variant names:

• chr20-45293994-G-C
• rs201738886
• NM_001393530.1:c.1601C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393530.1(MATN4):​c.1601C>G​(p.Thr534Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000767 in 1,602,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22681153).

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.1601C>G	p.Thr534Arg	missense	Exon 9 of 10	NP_001380459.1	O95460-2
	MATN4	NM_003833.5		c.1601C>G	p.Thr534Arg	missense	Exon 10 of 11	NP_003824.2
	MATN4	NM_001393531.1		c.1601C>G	p.Thr534Arg	missense	Exon 9 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.1601C>G	p.Thr534Arg	missense	Exon 9 of 10	ENSP00000361842.1	O95460-2
	MATN4	ENST00000372754.5	TSL:5	c.1724C>G	p.Thr575Arg	missense	Exon 9 of 10	ENSP00000361840.1	O95460-1
	MATN4	ENST00000360607.10	TSL:1	c.1478C>G	p.Thr493Arg	missense	Exon 8 of 9	ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000494 AC: 12 AN: 242712 AF XY: 0.0000606

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000972

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000800 AC: 116 AN: 1450390 Hom.: 0 Cov.: 32 AF XY: 0.0000928 AC XY: 67 AN XY: 722106

African (AFR) AF: 0.0000299 AC: 1 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000998 AC: 111 AN: 1111718

Other (OTH) AF: 0.0000663 AC: 4 AN: 60294

GnomAD4 genome AF: 0.0000459 AC: 7 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

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	Benign	0.084
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.38
Sift	Benign	0.10	T
Sift4G	Benign	0.51	T
Polyphen		0.91	P
Vest4		0.45
MVP		0.85
MPC		1.1
ClinPred		0.29	T
GERP RS		4.8
Varity_R		0.50
gMVP		0.74
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201738886; hg19: chr20-43922634;