dbSNP rs530914126: COL10A1:c.*315delA (chr6-116119757-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_000493.4(COL10A1):c.*315delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 219,326 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 0 hom. )

Consequence

COL10A1
NM_000493.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000561 (82/146190) while in subpopulation AFR AF = 0.00175 (70/39892). AF 95% confidence interval is 0.00142. There are 0 homozygotes in GnomAd4. There are 42 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 82 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL10A1	NM_000493.4 link	c.*315delA		3_prime_UTR_variant	Exon 3 of 3	ENST00000651968.1	NP_000484.2	Q03692A0A650AXN9
NT5DC1	NM_152729.3 link	c.529+1822delT		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.*315delA		3_prime_UTR_variant	Exon 3 of 3		NM_000493.4	ENSP00000498802.1		Q03692
NT5DC1	ENST00000319550.9 link	c.529+1822delT		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1

Frequencies

GnomAD3 genomes

AF:

0.000561

AC:

AN:

146098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000544

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000454

Gnomad OTH

AF:

0.000498

GnomAD4 exome

AF:

0.00503

AC:

368

AN:

73136

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

196

AN XY:

37120

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00559

AC:

AN:

2324

American (AMR)

AF:

0.00498

AC:

AN:

3814

Ashkenazi Jewish (ASJ)

AF:

0.00580

AC:

AN:

2588

East Asian (EAS)

AF:

0.00455

AC:

AN:

5494

South Asian (SAS)

AF:

0.00906

AC:

AN:

3312

European-Finnish (FIN)

AF:

0.00227

AC:

AN:

3526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

320

European-Non Finnish (NFE)

AF:

0.00503

AC:

236

AN:

46964

Other (OTH)

AF:

0.00459

AC:

AN:

4794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.243

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000561

AC:

AN:

146190

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

AN XY:

71138

show subpopulations

African (AFR)

AF:

0.00175

AC:

AN:

39892

American (AMR)

AF:

0.000543

AC:

AN:

14724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3338

East Asian (EAS)

AF:

0.00

AC:

AN:

4984

South Asian (SAS)

AF:

0.00

AC:

AN:

4482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000454

AC:

AN:

66134

Other (OTH)

AF:

0.000494

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

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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rs530914126

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over