chr6-116119047-C-T

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL10A1NM_000493.4 linkuse as main transcriptc.*1026G>A 3_prime_UTR_variant 3/3 ENST00000651968.1
NT5DC1NM_152729.3 linkuse as main transcriptc.529+1102C>T intron_variant ENST00000319550.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL10A1ENST00000651968.1 linkuse as main transcriptc.*1026G>A 3_prime_UTR_variant 3/3 NM_000493.4 P1
NT5DC1ENST00000319550.9 linkuse as main transcriptc.529+1102C>T intron_variant 1 NM_152729.3 P1Q5TFE4-1

Frequencies

GnomAD3 genomes
AF:
0.0513
AC:
7803
AN:
152070
Hom.:
229
Cov.:
33
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:
11
AN:
422
Hom.:
0
Cov.:
0
AF XY:
0.0354
AC XY:
9
AN XY:
254
show subpopulations
Gnomad4 FIN exome
AF:
0.0240
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.250
GnomAD4 genome
AF:
0.0513
AC:
7812
AN:
152188
Hom.:
230
Cov.:
33
AF XY:
0.0503
AC XY:
3744
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0612
Gnomad4 AMR
AF:
0.0399
Gnomad4 ASJ
AF:
0.0634
Gnomad4 EAS
AF:
0.0156
Gnomad4 SAS
AF:
0.0494
Gnomad4 FIN
AF:
0.0233
Gnomad4 NFE
AF:
0.0542
Gnomad4 OTH
AF:
0.0483
Alfa
AF:
0.0448
Hom.:
85
Bravo
AF:
0.0520
Asia WGS
AF:
0.0430
AC:
151
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Metaphyseal chondrodysplasia, Schmid type Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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
-0.77
CADD
Benign
1.6
DANN
Benign
0.75

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.

Other links and lift over

dbSNP: rs1059277; hg19: chr6-116440210; API