1-30723472-G-A

Variant names:

• chr1-30723472-G-A
• rs754224196
• NM_002379.3:c.80C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002379.3(MATN1):​c.80C>T​(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 1,370,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: MATN1 NM_002379.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07366899).

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.80C>T	p.Ala27Val	missense	Exon 1 of 8	NP_002370.1	P21941
	MATN1-AS1	NR_034182.1		n.1229+1750G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN1	ENST00000373765.5	TSL:1 MANE Select	c.80C>T	p.Ala27Val	missense	Exon 1 of 8	ENSP00000362870.4	P21941
	MATN1-AS1	ENST00000454613.2	TSL:1	n.1232+1750G>A		intron	N/A
	MATN1-AS1	ENST00000414532.6	TSL:2	n.3106+1750G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000776 AC: 1 AN: 128894 AF XY: 0.00

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: 0.0000199

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000657 AC: 9 AN: 1370704 Hom.: 0 Cov.: 31 AF XY: 0.00000296 AC XY: 2 AN XY: 675376

African (AFR) AF: 0.00 AC: 0 AN: 29640

American (AMR) AF: 0.00 AC: 0 AN: 30936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24364

East Asian (EAS) AF: 0.00 AC: 0 AN: 33222

South Asian (SAS) AF: 0.00 AC: 0 AN: 74854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5334

European-Non Finnish (NFE) AF: 0.00000750 AC: 8 AN: 1067254

Other (OTH) AF: 0.0000176 AC: 1 AN: 56890

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000193 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.47
DANN	Benign	0.49
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.35
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.035
Sift	Benign	0.45	T
Sift4G	Benign	0.29	T
Polyphen		0.43	B
Vest4		0.065
MutPred		0.28		Loss of disorder (P = 0.1179)
MVP		0.43
MPC		0.25
ClinPred		0.15	T
GERP RS		-1.3
PromoterAI		0.036	Neutral
Varity_R		0.027
gMVP		0.28
Mutation Taster		=87/13	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: rs754224196; hg19: chr1-31196319;