rs2228548

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000493.4(COL10A1):c.1809G>C(p.Val603Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,614,142 control chromosomes in the GnomAD database, including 2,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 167 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2527 hom. )

Consequence

COL10A1
NM_000493.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.102

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 6-116120307-C-G is Benign according to our data. Variant chr6-116120307-C-G is described in ClinVar as [Benign]. Clinvar id is 256261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.102 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL10A1	NM_000493.4 link	c.1809G>C	p.Val603Val	synonymous_variant	Exon 3 of 3	ENST00000651968.1	NP_000484.2	Q03692A0A650AXN9
NT5DC1	NM_152729.3 link	c.529+2362C>G		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.1809G>C	p.Val603Val	synonymous_variant	Exon 3 of 3		NM_000493.4	ENSP00000498802.1		Q03692
NT5DC1	ENST00000319550.9 link	c.529+2362C>G		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6743

AN:

152164

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0622

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.0562

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0585

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0436

AC:

10960

AN:

251476

Hom.:

287

AF XY:

0.0452

AC XY:

6147

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.0645

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0349

Gnomad FIN exome

AF:

0.0564

Gnomad NFE exome

AF:

0.0579

Gnomad OTH exome

AF:

0.0438

GnomAD4 exome

AF:

0.0556

AC:

81329

AN:

1461860

Hom.:

2527

Cov.:

AF XY:

0.0553

AC XY:

40181

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0642

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0365

Gnomad4 FIN exome

AF:

0.0577

Gnomad4 NFE exome

AF:

0.0611

Gnomad4 OTH exome

AF:

0.0527

GnomAD4 genome

AF:

0.0443

AC:

6748

AN:

152282

Hom.:

167

Cov.:

AF XY:

0.0426

AC XY:

3172

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0322

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.0622

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0364

Gnomad4 FIN

AF:

0.0562

Gnomad4 NFE

AF:

0.0585

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0558

Hom.:

207

Bravo

AF:

0.0416

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0551

EpiControl

AF:

0.0573

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Metaphyseal chondrodysplasia, Schmid type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.6

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over