6-116120483-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_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 (★★). Synonymous variant affecting the same amino acid position (i.e. G545G) has been classified as Likely 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

Publications

20 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL10A1	NM_000493.4	MANE Select	c.1633G>C	p.Gly545Arg	missense	Exon 3 of 3	NP_000484.2
NT5DC1	NM_152729.3	MANE Select	c.529+2538C>G		intron	N/A	NP_689942.2
COL10A1	NM_001424106.1		c.1633G>C	p.Gly545Arg	missense	Exon 3 of 3	NP_001411035.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL10A1	ENST00000651968.1	MANE Select	c.1633G>C	p.Gly545Arg	missense	Exon 3 of 3	ENSP00000498802.1
COL10A1	ENST00000243222.8	TSL:1	c.1633G>C	p.Gly545Arg	missense	Exon 3 of 3	ENSP00000243222.4
COL10A1	ENST00000327673.4	TSL:1	c.1633G>C	p.Gly545Arg	missense	Exon 2 of 2	ENSP00000327368.4

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

GnomAD2 exomes

AF:

0.143

AC:

36048

AN:

251254

AF XY:

0.144

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 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

African (AFR)

AF:

0.267

AC:

8936

AN:

33480

American (AMR)

AF:

0.0828

AC:

3702

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2722

AN:

26136

East Asian (EAS)

AF:

0.262

AC:

10382

AN:

39700

South Asian (SAS)

AF:

0.210

AC:

18080

AN:

86258

European-Finnish (FIN)

AF:

0.151

AC:

8080

AN:

53416

Middle Eastern (MID)

AF:

0.0876

AC:

505

AN:

5768

European-Non Finnish (NFE)

AF:

0.116

AC:

128932

AN:

1111994

Other (OTH)

AF:

0.138

AC:

8305

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10608

21215

31823

42430

53038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4866

9732

14598

19464

24330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.165

AC:

25124

AN:

152204

Hom.:

2509

Cov.:

AF XY:

0.168

AC XY:

12492

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.262

AC:

10879

AN:

41506

American (AMR)

AF:

0.101

AC:

1544

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

389

AN:

3470

East Asian (EAS)

AF:

0.223

AC:

1151

AN:

5170

South Asian (SAS)

AF:

0.224

AC:

1076

AN:

4812

European-Finnish (FIN)

AF:

0.149

AC:

1578

AN:

10620

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8122

AN:

68008

Other (OTH)

AF:

0.147

AC:

311

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1052

2104

3157

4209

5261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.112

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Metaphyseal chondrodysplasia, Schmid type (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0018

MetaSVM

Uncertain

0.54

MutationAssessor

Pathogenic

3.5

PhyloP100

5.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.56

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.016

Polyphen

0.97

Vest4

0.29

MutPred

0.48

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

Mutation Taster

=99/1

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

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over