Genetic Variant COL10A1:c.*315dupA (chr6-116119757-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000493.4(COL10A1):c.*315dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 219,046 control chromosomes in the GnomAD database, including 147 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.041 ( 137 hom., cov: 32)

Exomes 𝑓: 0.029 ( 10 hom. )

Consequence

COL10A1
NM_000493.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23

Publications

0 publications found

Variant links:

Genes affected

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 links:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-116119757-A-AT is Benign according to our data. Variant chr6-116119757-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 355082.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL10A1	NM_000493.4 link	c.*315dupA		3_prime_UTR_variant	Exon 3 of 3	ENST00000651968.1	NP_000484.2	Q03692A0A650AXN9
NT5DC1	NM_152729.3 link	c.529+1822dupT		intron_variant	Intron 6 of 11	ENST00000319550.9	NP_689942.2	Q5TFE4-1Q9H2R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL10A1	ENST00000651968.1 link	c.*315dupA		3_prime_UTR_variant	Exon 3 of 3		NM_000493.4	ENSP00000498802.1		Q03692
NT5DC1	ENST00000319550.9 link	c.529+1822dupT		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6016

AN:

146080

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0407

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.0343

GnomAD4 exome

AF:

0.0288

AC:

2101

AN:

72874

Hom.:

Cov.:

AF XY:

0.0298

AC XY:

1102

AN XY:

37036

show subpopulations

African (AFR)

AF:

0.0255

AC:

AN:

2314

American (AMR)

AF:

0.0190

AC:

AN:

3780

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

AN:

2580

East Asian (EAS)

AF:

0.0197

AC:

108

AN:

5474

South Asian (SAS)

AF:

0.0221

AC:

AN:

3310

European-Finnish (FIN)

AF:

0.0190

AC:

AN:

3518

Middle Eastern (MID)

AF:

0.0348

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0321

AC:

1504

AN:

46802

Other (OTH)

AF:

0.0305

AC:

146

AN:

4780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

175

262

350

437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0412

AC:

6022

AN:

146172

Hom.:

137

Cov.:

AF XY:

0.0406

AC XY:

2887

AN XY:

71126

show subpopulations

African (AFR)

AF:

0.0299

AC:

1191

AN:

39886

American (AMR)

AF:

0.0311

AC:

458

AN:

14724

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

136

AN:

3342

East Asian (EAS)

AF:

0.0169

AC:

AN:

4984

South Asian (SAS)

AF:

0.0494

AC:

221

AN:

4478

European-Finnish (FIN)

AF:

0.0272

AC:

256

AN:

9424

Middle Eastern (MID)

AF:

0.0174

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0535

AC:

3539

AN:

66122

Other (OTH)

AF:

0.0341

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

273

546

820

1093

1366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00997

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Metaphyseal chondrodysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism

(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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6-116119757-A-AT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over