Genetic Variant NM_000493.4:c.*327_*328dupAA (chr6-116119744-G-GTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000493.4(COL10A1):c.*327_*328dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COL10A1
NM_000493.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.606

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL10A1	NM_000493.4 link	c.327_328dupAA		3_prime_UTR_variant	Exon 3 of 3	ENST00000651968.1	NP_000484.2	Q03692A0A650AXN9
NT5DC1	NM_152729.3 link	c.529+1809_529+1810dupTT		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.327_328dupAA		3_prime_UTR_variant	Exon 3 of 3		NM_000493.4	ENSP00000498802.1		Q03692
NT5DC1	ENST00000319550.9 link	c.529+1809_529+1810dupTT		intron_variant	Intron 6 of 11	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138030

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000737

AC:

AN:

74646

Hom.:

Cov.:

AF XY:

0.000869

AC XY:

AN XY:

37960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000482

AC:

AN:

2074

American (AMR)

AF:

0.000758

AC:

AN:

3956

Ashkenazi Jewish (ASJ)

AF:

0.00163

AC:

AN:

2460

East Asian (EAS)

AF:

0.000975

AC:

AN:

5130

South Asian (SAS)

AF:

0.00339

AC:

AN:

4428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3472

Middle Eastern (MID)

AF:

0.00331

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.000519

AC:

AN:

48176

Other (OTH)

AF:

0.000215

AC:

AN:

4648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.241

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

138030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66976

African (AFR)

AF:

0.00

AC:

AN:

37502

American (AMR)

AF:

0.00

AC:

AN:

14078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3222

East Asian (EAS)

AF:

0.00

AC:

AN:

4650

South Asian (SAS)

AF:

0.00

AC:

AN:

4212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62560

Other (OTH)

AF:

0.00

AC:

AN:

1886

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_000493.4:c.327_328dupAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over