Genetic Variant NT5DC1:c.529+50442A>G (chr6-116168387-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152729.3(NT5DC1):c.529+50442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,796 control chromosomes in the GnomAD database, including 3,367 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 0.19 ( 3367 hom., cov: 32)

Consequence

NT5DC1
NM_152729.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158

Publications

2 publications found

Variant links:

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]

NT5DC1 links:

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)

COL10A1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3 link	c.529+50442A>G	intron_variant	Intron 6 of 11	ENST00000319550.9	NP_689942.2	Q5TFE4-1Q9H2R1
COL10A1	NM_001424107.1 link	c.-15-42880T>C	intron_variant	Intron 1 of 2		NP_001411036.1
COL10A1	XM_011535433.4 link	c.-16+40876T>C	intron_variant	Intron 1 of 2		XP_011533735.1	Q03692A0A650AXN9
NT5DC1	XM_006715378.4 link	c.529+50442A>G	intron_variant	Intron 6 of 9		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9 link	c.529+50442A>G		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1
NT5DC1	ENST00000460749.1 link	n.25+50442A>G		intron_variant	Intron 1 of 6	5		ENSP00000433238.1		H0YDA5

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28880

AN:

151678

Hom.:

3369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0622

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.224

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

GnomAD4 genome

AF:

0.190

AC:

28873

AN:

151796

Hom.:

3367

Cov.:

AF XY:

0.183

AC XY:

13592

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.0873

AC:

3620

AN:

41444

American (AMR)

AF:

0.194

AC:

2957

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

937

AN:

3468

East Asian (EAS)

AF:

0.00405

AC:

AN:

5184

South Asian (SAS)

AF:

0.0627

AC:

301

AN:

4802

European-Finnish (FIN)

AF:

0.207

AC:

2156

AN:

10400

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18147

AN:

67918

Other (OTH)

AF:

0.221

AC:

466

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1144

2288

3433

4577

5721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.205

Hom.:

1326

Bravo

AF:

0.189

Asia WGS

AF:

0.0400

AC:

141

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.7

(source)

DANN

Benign

0.69

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr6-116168387-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over