Variant 10-13233764-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145314.3(UCMA):c.95T>C(p.Met32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,613,882 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0055 ( 31 hom. )

Consequence

UCMA
NM_145314.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.304

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050503314).

BP6

Variant 10-13233764-A-G is Benign according to our data. Variant chr10-13233764-A-G is described in ClinVar as [Benign]. Clinvar id is 789201.Status of the report is criteria_provided_single_submitter, 1 stars.

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.95T>C	p.Met32Thr	missense_variant	2/5	ENST00000378681.8
UCMA	NM_001303118.2 linkuse as main transcript	c.95T>C	p.Met32Thr	missense_variant	2/4
UCMA	NM_001303119.2 linkuse as main transcript	c.58+437T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCMA	ENST00000378681.8 linkuse as main transcript	c.95T>C	p.Met32Thr	missense_variant	2/5	1	NM_145314.3	P1
UCMA	ENST00000463405.2 linkuse as main transcript	c.59-131T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

855

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00610

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00935

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00863

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00485

AC:

1219

AN:

251420

Hom.:

AF XY:

0.00458

AC XY:

623

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00929

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00549

AC:

8023

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

3897

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00365

Gnomad4 ASJ exome

AF:

0.00520

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00964

Gnomad4 NFE exome

AF:

0.00615

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.00562

AC:

855

AN:

152016

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

453

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00610

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00935

Gnomad4 NFE

AF:

0.00863

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00690

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.00472

AC:

573

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00486

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

Cadd

Benign

0.042

Dann

Benign

0.20

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.35

REVEL

Benign

0.019

Sift

Benign

0.63

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.10

MVP

0.030

MPC

0.067

ClinPred

0.0015

GERP RS

-4.1

Varity_R

0.082

gMVP

0.074

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