chr6-116120163-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_000493.4(COL10A1):​c.1953G>A​(p.Trp651*) variant causes a stop gained change involving the alteration of a non-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 Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

COL10A1
NM_000493.4 stop_gained

Scores

4
2
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 2.37

Publications

3 publications found
Variant links:
Genes affected
COL10A1 (HGNC:2185): (collagen type X alpha 1 chain) This gene encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X collagen is a homotrimer. Mutations in this gene are associated with Schmid type metaphyseal chondrodysplasia (SMCD) and Japanese type spondylometaphyseal dysplasia (SMD). [provided by RefSeq, Jul 2008]
NT5DC1 (HGNC:21556): (5'-nucleotidase domain containing 1) While the exact function of the protein encoded by this gene is not known, it belongs to the 5'(3')-deoxyribonucleotidase family. [provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 19 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-116120163-C-T is Pathogenic according to our data. Variant chr6-116120163-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 17473.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL10A1NM_000493.4 linkc.1953G>A p.Trp651* stop_gained Exon 3 of 3 ENST00000651968.1 NP_000484.2 Q03692A0A650AXN9
NT5DC1NM_152729.3 linkc.529+2218C>T intron_variant Intron 6 of 11 ENST00000319550.9 NP_689942.2 Q5TFE4-1Q9H2R1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL10A1ENST00000651968.1 linkc.1953G>A p.Trp651* stop_gained Exon 3 of 3 NM_000493.4 ENSP00000498802.1 Q03692
NT5DC1ENST00000319550.9 linkc.529+2218C>T intron_variant Intron 6 of 11 1 NM_152729.3 ENSP00000326858.3 Q5TFE4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Metaphyseal chondrodysplasia, Schmid type Pathogenic:2
Jan 01, 1995
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Juno Genomics, Hangzhou Juno Genomics, Inc
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

PM2_Supporting+PVS1_Strong+PS4_Supporting+PP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
39
DANN
Uncertain
0.99
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.94
D
PhyloP100
2.4
Vest4
0.80
GERP RS
5.0
Mutation Taster
=1/199
disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs111033547; hg19: chr6-116441326; API