6-116125413-A-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.80T>C(p.Met27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,613,516 control chromosomes in the GnomAD database, including 133,812 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M27R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.47 ( 18514 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115298 hom. )

Consequence

COL10A1
NM_000493.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.72

Publications

58 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=2.0376253E-6).

BP6

Variant 6-116125413-A-G is Benign according to our data. Variant chr6-116125413-A-G is described in ClinVar as Benign. ClinVar VariationId is 256262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 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.80T>C	p.Met27Thr	missense	Exon 2 of 3	NP_000484.2
NT5DC1	NM_152729.3	MANE Select	c.529+7468A>G		intron	N/A	NP_689942.2
COL10A1	NM_001424106.1		c.80T>C	p.Met27Thr	missense	Exon 2 of 3	NP_001411035.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL10A1	ENST00000651968.1	MANE Select	c.80T>C	p.Met27Thr	missense	Exon 2 of 3	ENSP00000498802.1
COL10A1	ENST00000243222.8	TSL:1	c.80T>C	p.Met27Thr	missense	Exon 2 of 3	ENSP00000243222.4
COL10A1	ENST00000327673.4	TSL:1	c.80T>C	p.Met27Thr	missense	Exon 1 of 2	ENSP00000327368.4

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70773

AN:

151934

Hom.:

18483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.452

GnomAD2 exomes

AF:

0.370

AC:

92932

AN:

251422

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.724

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.386

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.391

AC:

570913

AN:

1461464

Hom.:

115298

Cov.:

AF XY:

0.389

AC XY:

282484

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.723

AC:

24178

AN:

33454

American (AMR)

AF:

0.244

AC:

10919

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

11282

AN:

26122

East Asian (EAS)

AF:

0.270

AC:

10711

AN:

39628

South Asian (SAS)

AF:

0.345

AC:

29788

AN:

86242

European-Finnish (FIN)

AF:

0.364

AC:

19458

AN:

53408

Middle Eastern (MID)

AF:

0.364

AC:

2094

AN:

5760

European-Non Finnish (NFE)

AF:

0.394

AC:

437699

AN:

1111764

Other (OTH)

AF:

0.411

AC:

24784

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

19788

39576

59363

79151

98939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13736

27472

41208

54944

68680

<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:

0.466

AC:

70842

AN:

152052

Hom.:

18514

Cov.:

AF XY:

0.460

AC XY:

34194

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.715

AC:

29663

AN:

41470

American (AMR)

AF:

0.343

AC:

5248

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1479

AN:

3464

East Asian (EAS)

AF:

0.234

AC:

1209

AN:

5164

South Asian (SAS)

AF:

0.354

AC:

1707

AN:

4818

European-Finnish (FIN)

AF:

0.358

AC:

3788

AN:

10572

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26443

AN:

67968

Other (OTH)

AF:

0.452

AC:

954

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1719

3437

5156

6874

8593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.409

Hom.:

46489

Bravo

AF:

0.473

TwinsUK

AF:

0.390

AC:

1446

ALSPAC

AF:

0.399

AC:

1538

ESP6500AA

AF:

0.700

AC:

3084

ESP6500EA

AF:

0.393

AC:

3384

ExAC

AF:

0.380

AC:

46186

Asia WGS

AF:

0.392

AC:

1362

AN:

3478

EpiCase

AF:

0.387

EpiControl

AF:

0.390

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 (3)

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.18

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.10

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.69

PhyloP100

2.7

PrimateAI

Benign

0.46

PROVEAN

Benign

0.34

REVEL

Benign

0.27

Sift

Benign

1.0

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.095

MPC

0.0078

ClinPred

0.0050

GERP RS

6.1

PromoterAI

0.0080

Neutral

(source)

Varity_R

0.071

gMVP

0.36

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

Computational scores

Splicing

Publications

Other links and lift over