6-116119744-G-GT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000493.4(COL10A1):c.*328_*329insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 210,906 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.053 (0 hom.)
• Consequence: COL10A1 NM_000493.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.606

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL10A1	NM_000493.4	c.*328_*329insA		3_prime_UTR_variant	3/3	ENST00000651968.1
NT5DC1	NM_152729.3	c.529+1810dup		intron_variant		ENST00000319550.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL10A1	ENST00000651968.1	c.*328_*329insA		3_prime_UTR_variant	3/3		NM_000493.4	P1
NT5DC1	ENST00000319550.9	c.529+1810dup		intron_variant		1	NM_152729.3	P1

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 363 AN: 137918 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00192

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000861

Gnomad SAS AF: 0.00119

Gnomad FIN AF: 0.00229

Gnomad MID AF: 0.0204

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00265

GnomAD4 exome AF: 0.0531 AC: 3874 AN: 72928 Hom.: 0 Cov.: 0 AF XY: 0.0532 AC XY: 1970 AN XY: 37052

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.0659

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.0436

Gnomad4 FIN exome AF: 0.0429

Gnomad4 NFE exome AF: 0.0544

Gnomad4 OTH exome AF: 0.0504

GnomAD4 genome AF: 0.00263 AC: 363 AN: 137978 Hom.: 1 Cov.: 32 AF XY: 0.00266 AC XY: 178 AN XY: 66980

Gnomad4 AFR AF: 0.00426

Gnomad4 AMR AF: 0.00192

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000863

Gnomad4 SAS AF: 0.00119

Gnomad4 FIN AF: 0.00229

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Metaphyseal chondrodysplasia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs371155563; hg19: chr6-116440907;