Genetic Variant UCMA:c.320-80G>T (chr10-13222280-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145314.3(UCMA):c.320-80G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,336,252 control chromosomes in the GnomAD database, including 55,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7277 hom., cov: 31)

Exomes 𝑓: 0.27 ( 48265 hom. )

Consequence

UCMA
NM_145314.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

Publications

4 publications found

Variant links:

Genes affected

UCMA (HGNC:25205): (upper zone of growth plate and cartilage matrix associated) This gene encodes a chondrocyte-specific, highly charged protein that is abundantly expressed in the upper immature zone of fetal and juvenile epiphyseal cartilage. The encoded protein undergoes proteolytic processing to generate a mature protein that is secreted into the extracellular matrix. The glutamic acid residues in the encoded protein undergo gamma carboxylation in a vitamin K-dependent manner. Undercarboxylation of the encoded protein is associated with osteoarthritis in humans. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]

UCMA links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UCMA	NM_145314.3 link	c.320-80G>T	intron_variant	Intron 4 of 4	ENST00000378681.8	NP_660357.2
UCMA	NM_001303118.2 link	c.224-80G>T	intron_variant	Intron 3 of 3		NP_001290047.1
UCMA	NM_001303119.2 link	c.158-80G>T	intron_variant	Intron 2 of 2		NP_001290048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCMA	ENST00000378681.8 link	c.320-80G>T		intron_variant	Intron 4 of 4	1	NM_145314.3	ENSP00000367952.3
UCMA	ENST00000463405.2 link	c.254-80G>T		intron_variant	Intron 3 of 3	5		ENSP00000473368.1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45154

AN:

151974

Hom.:

7258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.299

GnomAD4 exome

AF:

0.272

AC:

322502

AN:

1184160

Hom.:

48265

AF XY:

0.275

AC XY:

163648

AN XY:

595032

show subpopulations

African (AFR)

AF:

0.287

AC:

8183

AN:

28548

American (AMR)

AF:

0.443

AC:

15929

AN:

35940

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

5967

AN:

22860

East Asian (EAS)

AF:

0.592

AC:

22065

AN:

37268

South Asian (SAS)

AF:

0.354

AC:

26353

AN:

74370

European-Finnish (FIN)

AF:

0.282

AC:

12914

AN:

45790

Middle Eastern (MID)

AF:

0.307

AC:

1489

AN:

4848

European-Non Finnish (NFE)

AF:

0.244

AC:

215108

AN:

883330

Other (OTH)

AF:

0.283

AC:

14494

AN:

51206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

11314

22627

33941

45254

56568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6900

13800

20700

27600

34500

<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:

0.297

AC:

45212

AN:

152092

Hom.:

7277

Cov.:

AF XY:

0.305

AC XY:

22649

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.289

AC:

11970

AN:

41482

American (AMR)

AF:

0.398

AC:

6073

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

913

AN:

3472

East Asian (EAS)

AF:

0.599

AC:

3097

AN:

5166

South Asian (SAS)

AF:

0.371

AC:

1790

AN:

4820

European-Finnish (FIN)

AF:

0.282

AC:

2979

AN:

10582

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17422

AN:

67986

Other (OTH)

AF:

0.296

AC:

622

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1607

3214

4821

6428

8035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.271

Hom.:

9125

Bravo

AF:

0.305

Asia WGS

AF:

0.482

AC:

1676

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.25

(source)

DANN

Benign

0.69

PhyloP100

-1.4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over