6-116120483-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_000493.4(COL10A1):c.1633G>C(p.Gly545Arg) variant causes a missense change. The variant allele was found at a frequency of 0.133 in 1,614,074 control chromosomes in the GnomAD database, including 16,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2509 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13957 hom. )

Consequence

COL10A1
NM_000493.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.10

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 -18 ACMG points.

PM1

In a region_of_interest Nonhelical region (NC1) (size 160) in uniprot entity COAA1_HUMAN there are 9 pathogenic changes around while only 1 benign (90%) in NM_000493.4

BP4

Computational evidence support a benign effect (MetaRNN=0.0018019676).

BP6

Variant 6-116120483-C-G is Benign according to our data. Variant chr6-116120483-C-G is described in ClinVar as [Benign]. Clinvar id is 256260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL10A1	NM_000493.4 link	c.1633G>C	p.Gly545Arg	missense_variant	Exon 3 of 3	ENST00000651968.1	NP_000484.2	Q03692A0A650AXN9
NT5DC1	NM_152729.3 link	c.529+2538C>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.1633G>C	p.Gly545Arg	missense_variant	Exon 3 of 3		NM_000493.4	ENSP00000498802.1		Q03692
NT5DC1	ENST00000319550.9 link	c.529+2538C>G		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25102

AN:

152086

Hom.:

2501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.143

AC:

36048

AN:

251254

Hom.:

3087

AF XY:

0.144

AC XY:

19633

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.0785

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.130

AC:

189644

AN:

1461870

Hom.:

13957

Cov.:

AF XY:

0.132

AC XY:

95731

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.0828

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.165

AC:

25124

AN:

152204

Hom.:

2509

Cov.:

AF XY:

0.168

AC XY:

12492

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.223

Gnomad4 SAS

AF:

0.224

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.112

Hom.:

860

Bravo

AF:

0.161

TwinsUK

AF:

0.117

AC:

433

ALSPAC

AF:

0.118

AC:

454

ESP6500AA

AF:

0.253

AC:

1113

ESP6500EA

AF:

0.114

AC:

980

ExAC

AF:

0.151

AC:

18381

EpiCase

AF:

0.106

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Metaphyseal chondrodysplasia, Schmid type

Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28651521) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

D;D

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;.

MetaRNN

Benign

0.0018

T;T

MetaSVM

Uncertain

0.54

MutationAssessor

Pathogenic

3.5

H;H

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.97

D;D

Vest4

0.29

MutPred

0.48

Loss of catalytic residue at V546 (P = 0.0513);Loss of catalytic residue at V546 (P = 0.0513);

MPC

0.045

ClinPred

0.044

GERP RS

4.8

Varity_R

0.22

gMVP

0.46

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