6-116119047-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000493.4(COL10A1):c.*1026G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 152,610 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (230 hom., cov: 33)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: COL10A1 NM_000493.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-116119047-C-T is Benign according to our data. Variant chr6-116119047-C-T is described in ClinVar as [Benign]. Clinvar id is 355069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL10A1	NM_000493.4	c.*1026G>A		3_prime_UTR_variant	3/3	ENST00000651968.1
NT5DC1	NM_152729.3	c.529+1102C>T		intron_variant		ENST00000319550.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL10A1	ENST00000651968.1	c.*1026G>A		3_prime_UTR_variant	3/3		NM_000493.4	P1
NT5DC1	ENST00000319550.9	c.529+1102C>T		intron_variant		1	NM_152729.3	P1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7803 AN: 152070 Hom.: 229 Cov.: 33

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.0261 AC: 11 AN: 422 Hom.: 0 Cov.: 0 AF XY: 0.0354 AC XY: 9 AN XY: 254

Gnomad4 FIN exome AF: 0.0240

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0513 AC: 7812 AN: 152188 Hom.: 230 Cov.: 33 AF XY: 0.0503 AC XY: 3744 AN XY: 74404

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0233

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0448 Hom.: 85

Bravo AF: 0.0520

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Metaphyseal chondrodysplasia, Schmid type Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.6
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs1059277; hg19: chr6-116440210;