20-45304381-G-C

Position:

• chr20-45304381-G-C

Variant summary

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

The NM_001393530.1(MATN4):​c.490C>G​(p.Arg164Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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=0.28568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN4	NM_001393530.1	c.490C>G	p.Arg164Gly	missense_variant	3/10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6	c.490C>G	p.Arg164Gly	missense_variant	3/10	1	NM_001393530.1	ENSP00000361842.1
MATN4	ENST00000372754.5	c.490C>G	p.Arg164Gly	missense_variant	2/10	5		ENSP00000361840.1
MATN4	ENST00000360607.10	c.490C>G	p.Arg164Gly	missense_variant	3/9	1		ENSP00000353819.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	.;T;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.67	.;T;T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	0.73	N;N;N;.;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.74	N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.099	.;.;T;T;.
Sift4G	Uncertain	0.044	D;D;D;T;D
Polyphen		0.13	B;.;P;P;B
Vest4		0.37
MutPred		0.53		Loss of MoRF binding (P = 0.018);Loss of MoRF binding (P = 0.018);Loss of MoRF binding (P = 0.018);Loss of MoRF binding (P = 0.018);Loss of MoRF binding (P = 0.018);
MVP		0.88
MPC		0.57
ClinPred		0.64	D
GERP RS		3.8
Varity_R		0.61
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072788; hg19: chr20-43933021;