Genetic Variant NM_000493.4:c.*1026G>A (chr6-116119047-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000493.4(COL10A1):c.*1026G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 152,610 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.051 ( 230 hom., cov: 33)

Exomes 𝑓: 0.026 ( 0 hom. )

Consequence

COL10A1
NM_000493.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-116119047-C-T is Benign according to our data. Variant chr6-116119047-C-T is described in ClinVar as Benign. ClinVar VariationId is 355069.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 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	Effect	Exon Rank	Protein	UniProt
COL10A1	NM_000493.4	MANE Select	c.*1026G>A	3_prime_UTR	Exon 3 of 3	NP_000484.2
NT5DC1	NM_152729.3	MANE Select	c.529+1102C>T	intron	N/A	NP_689942.2
COL10A1	NM_001424106.1		c.*1026G>A	3_prime_UTR	Exon 3 of 3	NP_001411035.1	A0A650AXN9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL10A1	ENST00000651968.1	MANE Select	c.*1026G>A	3_prime_UTR	Exon 3 of 3	ENSP00000498802.1	Q03692
COL10A1	ENST00000243222.8	TSL:1	c.*1026G>A	3_prime_UTR	Exon 3 of 3	ENSP00000243222.4	Q03692
COL10A1	ENST00000327673.4	TSL:1	c.*1026G>A	3_prime_UTR	Exon 2 of 2	ENSP00000327368.4	Q03692

Frequencies

GnomAD3 genomes

AF:

0.0513

AC:

7803

AN:

152070

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0400

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0489

GnomAD4 exome

AF:

0.0261

AC:

AN:

422

Hom.:

Cov.:

AF XY:

0.0354

AC XY:

AN XY:

254

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0240

AC:

AN:

416

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0513

AC:

7812

AN:

152188

Hom.:

230

Cov.:

AF XY:

0.0503

AC XY:

3744

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0612

AC:

2542

AN:

41530

American (AMR)

AF:

0.0399

AC:

610

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3472

East Asian (EAS)

AF:

0.0156

AC:

AN:

5190

South Asian (SAS)

AF:

0.0494

AC:

238

AN:

4822

European-Finnish (FIN)

AF:

0.0233

AC:

246

AN:

10578

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0542

AC:

3688

AN:

68002

Other (OTH)

AF:

0.0483

AC:

102

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

392

784

1176

1568

1960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0462

Hom.:

101

Bravo

AF:

0.0520

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Metaphyseal chondrodysplasia, Schmid type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

(source)

DANN

Benign

0.75

PhyloP100

-0.025

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over