1-30714321-T-A

Position:

• chr1-30714321-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000373765.5(MATN1):​c.1367A>T​(p.Asp456Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MATN1 ENST00000373765.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77

Genes affected

MATN1 (HGNC:6907): (matrilin 1) This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. Mutations of this gene have been associated with variety of inherited chondrodysplasias. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN1	NM_002379.3	c.1367A>T	p.Asp456Val	missense_variant	7/8	ENST00000373765.5	NP_002370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN1	ENST00000373765.5	c.1367A>T	p.Asp456Val	missense_variant	7/8	1	NM_002379.3	ENSP00000362870	P1
MATN1	ENST00000494561.1	n.387A>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.1367A>T (p.D456V) alteration is located in exon 7 (coding exon 7) of the MATN1 gene. This alteration results from a A to T substitution at nucleotide position 1367, causing the aspartic acid (D) at amino acid position 456 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.64
Sift	Benign	0.034	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.60		Loss of catalytic residue at D456 (P = 0.0326);
MVP		0.92
MPC		1.0
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-31187168;