rs779413744

Variant names:

• chr2-20006016-G-A
• rs779413744
• NM_002381.5:c.518C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-20006016-G-A
• chr2-20006016-G-C
• chr2-20006016-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_002381.5(MATN3):​c.518C>T​(p.Ala173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A173G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: MATN3 NM_002381.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210
• Publications: 6 publications found

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]

MATN3 Gene-Disease associations (from GenCC):

• multiple epiphyseal dysplasia type 5

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia, matrilin-3 type

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17486206).
• BP6: Variant 2-20006016-G-A is Benign according to our data. Variant chr2-20006016-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2411438.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002381.5. 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
	MATN3	NM_002381.5	MANE Select	c.518C>T	p.Ala173Val	missense	Exon 2 of 8	NP_002372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN3	ENST00000407540.8	TSL:1 MANE Select	c.518C>T	p.Ala173Val	missense	Exon 2 of 8	ENSP00000383894.3
	MATN3	ENST00000421259.2	TSL:1	c.518C>T	p.Ala173Val	missense	Exon 2 of 7	ENSP00000398753.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249252 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461704 Hom.: 0 Cov.: 61 AF XY: 0.00000963 AC XY: 7 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.8
DANN	Benign	0.95
DEOGEN2	Benign	0.38	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.21
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.10	B
Vest4		0.17
MutPred		0.75		Loss of disorder (P = 0.0877)
MVP		0.65
MPC		0.20
ClinPred		0.046	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.70
Mutation Taster		=61/39	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: rs779413744; hg19: chr2-20205777;