rs11965969

Variant names:

• chr6-116131040-T-G
• rs11965969
• NM_152729.3:c.529+13095T>G

Variant summary

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

The NM_152729.3(NT5DC1):​c.529+13095T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,978 control chromosomes in the GnomAD database, including 19,593 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 (19593 hom., cov: 32)
• Consequence: NT5DC1 NM_152729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 6 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, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3	c.529+13095T>G		intron_variant	Intron 6 of 11	ENST00000319550.9	NP_689942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9	c.529+13095T>G		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3
NT5DC1	ENST00000419791.3	c.529+13095T>G		intron_variant	Intron 6 of 6	3		ENSP00000393578.1
COL10A1	ENST00000418500.1	c.-15-5533A>C		intron_variant	Intron 1 of 1	3		ENSP00000392712.1
NT5DC1	ENST00000460749.1	n.25+13095T>G		intron_variant	Intron 1 of 6	5		ENSP00000433238.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75766 AN: 151860 Hom.: 19563 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.499 AC: 75844 AN: 151978 Hom.: 19593 Cov.: 32 AF XY: 0.495 AC XY: 36763 AN XY: 74274

African (AFR) AF: 0.632 AC: 26174 AN: 41438

American (AMR) AF: 0.486 AC: 7421 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1934 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1474 AN: 5182

South Asian (SAS) AF: 0.421 AC: 2029 AN: 4814

European-Finnish (FIN) AF: 0.420 AC: 4436 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30844 AN: 67944

Other (OTH) AF: 0.506 AC: 1070 AN: 2114

Alfa AF: 0.473 Hom.: 20812

Bravo AF: 0.511

Asia WGS AF: 0.441 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.58
DANN	Benign	0.69
PhyloP100		-0.44
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: rs11965969; hg19: chr6-116452203;