rs1546943

Variant names:

• chr6-116180340-G-A
• rs1546943
• NM_152729.3:c.530-40714G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152729.3(NT5DC1):​c.530-40714G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,806 control chromosomes in the GnomAD database, including 20,320 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 0.50 (20320 hom., cov: 32)
• Consequence: NT5DC1 NM_152729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 4 publications found

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]

COL10A1 Gene-Disease associations (from GenCC):

• Schmid metaphyseal chondrodysplasia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152729.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5DC1	NM_152729.3	MANE Select	c.530-40714G>A		intron	N/A	NP_689942.2
	COL10A1	NM_001424107.1		c.-16+36631C>T		intron	N/A	NP_001411036.1	A0A650AXN9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5DC1	ENST00000319550.9	TSL:1 MANE Select	c.530-40714G>A		intron	N/A	ENSP00000326858.3	Q5TFE4-1
	NT5DC1	ENST00000880964.1		c.530-40714G>A		intron	N/A	ENSP00000551023.1
	NT5DC1	ENST00000880963.1		c.530-40738G>A		intron	N/A	ENSP00000551022.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76380 AN: 151688 Hom.: 20290 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.508

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.504 AC: 76460 AN: 151806 Hom.: 20320 Cov.: 32 AF XY: 0.498 AC XY: 36966 AN XY: 74210

African (AFR) AF: 0.683 AC: 28311 AN: 41472

American (AMR) AF: 0.492 AC: 7510 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1862 AN: 3462

East Asian (EAS) AF: 0.274 AC: 1415 AN: 5168

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4816

European-Finnish (FIN) AF: 0.405 AC: 4275 AN: 10544

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 29955 AN: 67788

Other (OTH) AF: 0.506 AC: 1064 AN: 2102

Alfa AF: 0.466 Hom.: 20799

Bravo AF: 0.521

Asia WGS AF: 0.383 AC: 1326 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1546943; hg19: chr6-116501503; COSMIC: COSV60312032;