20-45304381-G-C

Variant names:

• chr20-45304381-G-C
• rs2072788
• NM_001393530.1:c.490C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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 Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MATN4 NM_001393530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 23 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28568).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN4	NM_001393530.1	MANE Select	c.490C>G	p.Arg164Gly	missense	Exon 3 of 10	NP_001380459.1
	MATN4	NM_003833.5		c.490C>G	p.Arg164Gly	missense	Exon 4 of 11	NP_003824.2
	MATN4	NM_001393531.1		c.490C>G	p.Arg164Gly	missense	Exon 3 of 9	NP_001380460.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN4	ENST00000372756.6	TSL:1 MANE Select	c.490C>G	p.Arg164Gly	missense	Exon 3 of 10	ENSP00000361842.1
	MATN4	ENST00000372754.5	TSL:5	c.490C>G	p.Arg164Gly	missense	Exon 2 of 10	ENSP00000361840.1
	MATN4	ENST00000360607.10	TSL:1	c.490C>G	p.Arg164Gly	missense	Exon 3 of 9	ENSP00000353819.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	0.73	N
PhyloP100		2.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.74	N
REVEL	Uncertain	0.35
Sift	Benign	0.099	T
Sift4G	Uncertain	0.044	D
Polyphen		0.13	B
Vest4		0.37
MutPred		0.53		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
Mutation Taster		=92/8	polymorphism

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: rs2072788; hg19: chr20-43933021;