rs3812111

Positions:

• chr6-116122572-T-A
• chr6-116122572-T-C
• chr6-116122572-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000493.4(COL10A1):​c.155-611A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,960 control chromosomes in the GnomAD database, including 18,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.47 (18498 hom., cov: 32)
• Consequence: COL10A1 NM_000493.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.479

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL10A1	NM_000493.4	c.155-611A>T		intron_variant		ENST00000651968.1	NP_000484.2
NT5DC1	NM_152729.3	c.529+4627T>A		intron_variant		ENST00000319550.9	NP_689942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9	c.529+4627T>A		intron_variant		1	NM_152729.3	ENSP00000326858	P1
COL10A1	ENST00000651968.1	c.155-611A>T		intron_variant			NM_000493.4	ENSP00000498802	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70735 AN: 151842 Hom.: 18467 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.466 AC: 70804 AN: 151960 Hom.: 18498 Cov.: 32 AF XY: 0.460 AC XY: 34171 AN XY: 74276

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.451

Alfa AF: 0.420 Hom.: 1717

Bravo AF: 0.473

Asia WGS AF: 0.389 AC: 1349 AN: 3476

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3812111; hg19: chr6-116443735; COSMIC: COSV54574409; COSMIC: COSV54574409;