Variant 10-13222107-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145314.3(UCMA):c.413C>G(p.Thr138Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,614,144 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0060 ( 36 hom. )

Consequence

UCMA
NM_145314.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.56

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005598396).

BS2

High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UCMA	NM_145314.3 linkuse as main transcript	c.413C>G	p.Thr138Ser	missense_variant	5/5	ENST00000378681.8
UCMA	NM_001303118.2 linkuse as main transcript	c.317C>G	p.Thr106Ser	missense_variant	4/4
UCMA	NM_001303119.2 linkuse as main transcript	c.251C>G	p.Thr84Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCMA	ENST00000378681.8 linkuse as main transcript	c.413C>G	p.Thr138Ser	missense_variant	5/5	1	NM_145314.3	P1
UCMA	ENST00000463405.2 linkuse as main transcript	c.347C>G	p.Thr116Ser	missense_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

718

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00789

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00531

AC:

1333

AN:

251214

Hom.:

AF XY:

0.00530

AC XY:

719

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00929

Gnomad NFE exome

AF:

0.00874

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00600

AC:

8778

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

4403

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00869

Gnomad4 NFE exome

AF:

0.00701

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.00471

AC:

718

AN:

152320

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00789

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00685

Hom.:

Bravo

AF:

0.00386

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.00591

AC:

717

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00735

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Keratoconus

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Apr 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Benign

0.89

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.043

Sift

Uncertain

0.0060

D;.

Polyphen

0.0

B;.

Vest4

0.061

MutPred

0.22

Gain of glycosylation at T138 (P = 0.0395);.;

MVP

0.040

MPC

0.062

ClinPred

0.011

GERP RS

2.6

Varity_R

0.087

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over