6-116120232-G-C

Variant names:

• chr6-116120232-G-C
• rs111033543
• NM_000493.4:c.1884C>G

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000493.4(COL10A1):​c.1884C>G​(p.Tyr628*) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL10A1 NM_000493.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.428
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Pathogenic. The variant received 11 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 31 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-116120232-G-C is Pathogenic according to our data. Variant chr6-116120232-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 17472.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL10A1	NM_000493.4	MANE Select	c.1884C>G	p.Tyr628*	stop_gained	Exon 3 of 3	NP_000484.2
	NT5DC1	NM_152729.3	MANE Select	c.529+2287G>C		intron	N/A	NP_689942.2
	COL10A1	NM_001424106.1		c.1884C>G	p.Tyr628*	stop_gained	Exon 3 of 3	NP_001411035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL10A1	ENST00000651968.1	MANE Select	c.1884C>G	p.Tyr628*	stop_gained	Exon 3 of 3	ENSP00000498802.1
	COL10A1	ENST00000243222.8	TSL:1	c.1884C>G	p.Tyr628*	stop_gained	Exon 3 of 3	ENSP00000243222.4
	COL10A1	ENST00000327673.4	TSL:1	c.1884C>G	p.Tyr628*	stop_gained	Exon 2 of 2	ENSP00000327368.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Metaphyseal chondrodysplasia, Schmid type Pathogenic:1

Jan 01, 1995

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	32
DANN	Benign	0.97
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		0.43
Vest4		0.79
GERP RS		-4.7
Mutation Taster		=2/198	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

Other links and lift over

dbSNP: rs111033543; hg19: chr6-116441395;