chr6-116120066-T-TGGGGTGTACAAGATTTAGATTAGCTCTGTGGG

Variant names:

• chr6-116120066-T-TGGGGTGTACAAGATTTAGATTAGCTCTGTGGG
• rs140722
• NM_000493.4:c.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC

Variant summary

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

The NM_000493.4(COL10A1):​c.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: COL10A1 NM_000493.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

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.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC		3_prime_UTR	Exon 3 of 3	NP_000484.2
	NT5DC1	NM_152729.3	MANE Select	c.529+2122_529+2123insGGGTGTACAAGATTTAGATTAGCTCTGTGGGG		intron	N/A	NP_689942.2
	COL10A1	NM_001424106.1		c.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC		3_prime_UTR	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.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC		3_prime_UTR	Exon 3 of 3	ENSP00000498802.1
	COL10A1	ENST00000243222.8	TSL:1	c.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC		3_prime_UTR	Exon 3 of 3	ENSP00000243222.4
	COL10A1	ENST00000327673.4	TSL:1	c.*6_*7insCCCACAGAGCTAATCTAAATCTTGTACACCCC		3_prime_UTR	Exon 2 of 2	ENSP00000327368.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140722; hg19: chr6-116441229;