chr1-30716213-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002379.3(MATN1):c.903C>G(p.Ile301Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I301I) has been classified as Benign.
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 1 hom. )
Consequence
MATN1
NM_002379.3 missense
NM_002379.3 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: -0.540
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]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
MATN1 | NM_002379.3 | c.903C>G | p.Ile301Met | missense_variant | 5/8 | ENST00000373765.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MATN1 | ENST00000373765.5 | c.903C>G | p.Ile301Met | missense_variant | 5/8 | 1 | NM_002379.3 | P1 | |
MATN1 | ENST00000477320.1 | n.756C>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251402Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135888
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GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461868Hom.: 1 Cov.: 35 AF XY: 0.0000536 AC XY: 39AN XY: 727232
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.903C>G (p.I301M) alteration is located in exon 5 (coding exon 5) of the MATN1 gene. This alteration results from a C to G substitution at nucleotide position 903, causing the isoleucine (I) at amino acid position 301 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of methylation at K296 (P = 0.2017);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at