6-116119757-A-AT

Position:

• chr6-116119757-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000493.4(COL10A1):​c.*315dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 219,046 control chromosomes in the GnomAD database, including 147 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (137 hom., cov: 32)
  • Exomes 𝑓: 0.029 (10 hom.)
• Consequence: COL10A1 NM_000493.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23

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 -10 ACMG points.

• BP6: Variant 6-116119757-A-AT is Benign according to our data. Variant chr6-116119757-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 355082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL10A1	NM_000493.4	c.*315dupA		3_prime_UTR_variant	3/3	ENST00000651968.1	NP_000484.2
NT5DC1	NM_152729.3	c.529+1822dupT		intron_variant		ENST00000319550.9	NP_689942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL10A1	ENST00000651968	c.*315dupA		3_prime_UTR_variant	3/3		NM_000493.4	ENSP00000498802.1
NT5DC1	ENST00000319550.9	c.529+1822dupT		intron_variant		1	NM_152729.3	ENSP00000326858.3

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6016 AN: 146080 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.0407

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0343

GnomAD4 exome AF: 0.0288 AC: 2101 AN: 72874 Hom.: 10 Cov.: 0 AF XY: 0.0298 AC XY: 1102 AN XY: 37036

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0236

Gnomad4 EAS exome AF: 0.0197

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0412 AC: 6022 AN: 146172 Hom.: 137 Cov.: 32 AF XY: 0.0406 AC XY: 2887 AN XY: 71126

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.0407

Gnomad4 EAS AF: 0.0169

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0341

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Metaphyseal chondrodysplasia Benign:1

Likely benign, 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: rs530914126; hg19: chr6-116440920;