6-116119744-GT-G

Position:

• chr6-116119744-GT-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_000493.4(COL10A1):​c.*328delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 212,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000239 (33/138068) while in subpopulation EAS AF= 0.00108 (5/4638). AF 95% confidence interval is 0.000424. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL10A1	NM_000493.4	c.*328delA		3_prime_UTR_variant	3/3	ENST00000651968.1	NP_000484.2
NT5DC1	NM_152729.3	c.529+1810delT		intron_variant		ENST00000319550.9	NP_689942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL10A1	ENST00000651968	c.*328delA		3_prime_UTR_variant	3/3		NM_000493.4	ENSP00000498802.1
NT5DC1	ENST00000319550.9	c.529+1810delT		intron_variant		1	NM_152729.3	ENSP00000326858.3

Frequencies

GnomAD3 genomes AF: 0.000239 AC: 33 AN: 138008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000213

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00108

Gnomad SAS AF: 0.000237

Gnomad FIN AF: 0.000114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000224

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00576 AC: 427 AN: 74118 Hom.: 0 Cov.: 0 AF XY: 0.00565 AC XY: 213 AN XY: 37680

Gnomad4 AFR exome AF: 0.00291

Gnomad4 AMR exome AF: 0.00612

Gnomad4 ASJ exome AF: 0.00448

Gnomad4 EAS exome AF: 0.00944

Gnomad4 SAS exome AF: 0.00638

Gnomad4 FIN exome AF: 0.00637

Gnomad4 NFE exome AF: 0.00552

Gnomad4 OTH exome AF: 0.00519

GnomAD4 genome AF: 0.000239 AC: 33 AN: 138068 Hom.: 0 Cov.: 32 AF XY: 0.000164 AC XY: 11 AN XY: 67042

Gnomad4 AFR AF: 0.000239

Gnomad4 AMR AF: 0.000213

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00108

Gnomad4 SAS AF: 0.000239

Gnomad4 FIN AF: 0.000114

Gnomad4 NFE AF: 0.000224

Gnomad4 OTH AF: 0.00

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;