6-116126193-C-G

Position:

• chr6-116126193-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152729.3(NT5DC1):​c.529+8248C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,106 control chromosomes in the GnomAD database, including 5,754 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5752 hom., cov: 32)
  • Exomes 𝑓: 0.20 (2 hom.)
• Consequence: NT5DC1 NM_152729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5DC1	NM_152729.3	c.529+8248C>G		intron_variant		ENST00000319550.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5DC1	ENST00000319550.9	c.529+8248C>G		intron_variant		1	NM_152729.3	P1
COL10A1	ENST00000418500.1	c.-15-686G>C		intron_variant		3
NT5DC1	ENST00000419791.3	c.529+8248C>G		intron_variant		3
NT5DC1	ENST00000460749.1	c.27+8248C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40103 AN: 151934 Hom.: 5746 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.204 AC: 11 AN: 54 Hom.: 2 AF XY: 0.229 AC XY: 11 AN XY: 48

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.264 AC: 40138 AN: 152052 Hom.: 5752 Cov.: 32 AF XY: 0.256 AC XY: 19014 AN XY: 74354

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0855

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.277

Alfa AF: 0.121 Hom.: 194

Bravo AF: 0.273

Asia WGS AF: 0.0680 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.67

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: rs9488843; hg19: chr6-116447356; COSMIC: COSV54574434; COSMIC: COSV54574434;