NM_145314.3:c.95T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 15/20 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.304

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 789201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCMA	NM_145314.3 link	c.95T>C	p.Met32Thr	missense_variant	Exon 2 of 5	ENST00000378681.8	NP_660357.2	Q8WVF2A0A067XJX6
UCMA	NM_001303118.2 link	c.95T>C	p.Met32Thr	missense_variant	Exon 2 of 4		NP_001290047.1	Q8WVF2A0A067XJP8
UCMA	NM_001303119.2 link	c.58+437T>C		intron_variant	Intron 1 of 2		NP_001290048.1	Q8WVF2A0A067XKV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCMA	ENST00000378681.8 link	c.95T>C	p.Met32Thr	missense_variant	Exon 2 of 5	1	NM_145314.3	ENSP00000367952.3		Q8WVF2
UCMA	ENST00000463405.2 link	c.59-131T>C		intron_variant	Intron 1 of 3	5		ENSP00000473368.1		R4GMV7

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

GnomAD2 exomes

AF:

0.00485

AC:

1219

AN:

251420

AF XY:

0.00458

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 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

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.00365

AC:

163

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00520

AC:

136

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000278

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00964

AC:

515

AN:

53410

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00615

AC:

6843

AN:

1112006

Other (OTH)

AF:

0.00525

AC:

317

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

476

952

1428

1904

2380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<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:

0.00562

AC:

855

AN:

152016

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

453

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.000844

AC:

AN:

41446

American (AMR)

AF:

0.00610

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3468

East Asian (EAS)

AF:

0.000389

AC:

AN:

5136

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00935

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00863

AC:

587

AN:

67980

Other (OTH)

AF:

0.00712

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00649

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

-0.30

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

Mutation Taster

=95/5

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over