chr2-20005919-C-G

Position:

• chr2-20005919-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002381.5(MATN3):​c.615G>C​(p.Glu205Asp) 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. 14/21 in silico tools predict 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: 32)
• Consequence: MATN3 NM_002381.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

Genes affected

MATN3 (HGNC:6909): (matrilin 3) This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This protein contains two von Willebrand factor A domains; it is present in the cartilage extracellular matrix and has a role in the development and homeostasis of cartilage and bone. Mutations in this gene result in multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain VWFA (size 175) in uniprot entity MATN3_HUMAN there are 27 pathogenic changes around while only 1 benign (96%) in NM_002381.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21968386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN3	NM_002381.5	c.615G>C	p.Glu205Asp	missense_variant	2/8	ENST00000407540.8	NP_002372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN3	ENST00000407540.8	c.615G>C	p.Glu205Asp	missense_variant	2/8	1	NM_002381.5	ENSP00000383894.3
MATN3	ENST00000421259.2	c.615G>C	p.Glu205Asp	missense_variant	2/7	1		ENSP00000398753.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.040	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.26
Sift	Benign	0.19	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.51	P;.
Vest4		0.18
MutPred		0.67		Gain of disorder (P = 0.2207);Gain of disorder (P = 0.2207);
MVP		0.99
MPC		0.17
ClinPred		0.76	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.60

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: rs28401180; hg19: chr2-20205680;