Genetic Variant NT5DC1:c.529+22530C>T (chr6-116140475-C-T) – 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+22530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,012 control chromosomes in the GnomAD database, including 2,182 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 0.14 ( 2182 hom., cov: 32)

Consequence

NT5DC1
NM_152729.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NT5DC1	NM_152729.3	MANE Select	c.529+22530C>T	intron	N/A	NP_689942.2
COL10A1	NM_001424106.1		c.-15-14968G>A	intron	N/A	NP_001411035.1
COL10A1	NM_001424107.1		c.-15-14968G>A	intron	N/A	NP_001411036.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NT5DC1	ENST00000319550.9	TSL:1 MANE Select	c.529+22530C>T	intron	N/A	ENSP00000326858.3
NT5DC1	ENST00000419791.3	TSL:3	c.530-4963C>T	intron	N/A	ENSP00000393578.1
COL10A1	ENST00000418500.1	TSL:3	c.-15-14968G>A	intron	N/A	ENSP00000392712.1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21804

AN:

151894

Hom.:

2182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.176

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

GnomAD4 genome

AF:

0.143

AC:

21801

AN:

152012

Hom.:

2182

Cov.:

AF XY:

0.136

AC XY:

10106

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0428

AC:

1772

AN:

41442

American (AMR)

AF:

0.159

AC:

2424

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3468

East Asian (EAS)

AF:

0.00231

AC:

AN:

5186

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4826

European-Finnish (FIN)

AF:

0.123

AC:

1303

AN:

10552

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.217

AC:

14721

AN:

67966

Other (OTH)

AF:

0.173

AC:

365

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

916

1831

2747

3662

4578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.198

Hom.:

1867

Bravo

AF:

0.147

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.16

(source)

DANN

Benign

0.16

PhyloP100

-1.5

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over