1-30716910-A-G

Position:

• chr1-30716910-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000373765.5(MATN1):​c.670T>C​(p.Ser224Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MATN1 ENST00000373765.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN1	NM_002379.3	c.670T>C	p.Ser224Pro	missense_variant	4/8	ENST00000373765.5	NP_002370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN1	ENST00000373765.5	c.670T>C	p.Ser224Pro	missense_variant	4/8	1	NM_002379.3	ENSP00000362870	P1
MATN1	ENST00000477320.1	n.523T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460474 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000519 Hom.: 0

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

Feb 06, 2024

The c.670T>C (p.S224P) alteration is located in exon 4 (coding exon 4) of the MATN1 gene. This alteration results from a T to C substitution at nucleotide position 670, causing the serine (S) at amino acid position 224 to be replaced by a proline (P). 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	0.13
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.20
Sift	Benign	0.24	T
Sift4G	Benign	0.13	T
Polyphen		0.017	B
Vest4		0.78
MutPred		0.58		Loss of catalytic residue at S224 (P = 0.2249);
MVP		0.81
MPC		0.31
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.24
gMVP		0.86

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: rs1639626103; hg19: chr1-31189757;