1-30721637-G-T

Variant names:

• chr1-30721637-G-T
• rs760462882
• NM_002379.3:c.209C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002379.3(MATN1):​c.209C>A​(p.Ser70*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MATN1 NM_002379.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 1 publications found

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]

MATN1-AS1 (HGNC:40364): (MATN1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002379.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN1	NM_002379.3	MANE Select	c.209C>A	p.Ser70*	stop_gained	Exon 2 of 8	NP_002370.1	P21941
	MATN1-AS1	NR_034182.1		n.1144G>T		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN1	ENST00000373765.5	TSL:1 MANE Select	c.209C>A	p.Ser70*	stop_gained	Exon 2 of 8	ENSP00000362870.4	P21941
	MATN1-AS1	ENST00000454613.2	TSL:1	n.1147G>T		non_coding_transcript_exon	Exon 2 of 4
	MATN1-AS1	ENST00000414532.6	TSL:2	n.3021G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249156 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000897

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461168 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726880

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52718

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		2.8
Vest4		0.81
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=45/155	disease causing (fs/PTC)

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: rs760462882; hg19: chr1-31194484;