dbSNP rs80070283: UCMA:p.Val101Ala (chr10-13229628-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145314.3(UCMA):c.302T>C(p.Val101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,613,968 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00035 ( 5 hom. )

Consequence

UCMA
NM_145314.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006891668).

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.302T>C	p.Val101Ala	missense_variant	Exon 4 of 5	ENST00000378681.8	NP_660357.2	Q8WVF2A0A067XJX6
UCMA	NM_001303118.2 link	c.206T>C	p.Val69Ala	missense_variant	Exon 3 of 4		NP_001290047.1	Q8WVF2A0A067XJP8
UCMA	NM_001303119.2 link	c.140T>C	p.Val47Ala	missense_variant	Exon 2 of 3		NP_001290048.1	Q8WVF2A0A067XKV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCMA	ENST00000378681.8 link	c.302T>C	p.Val101Ala	missense_variant	Exon 4 of 5	1	NM_145314.3	ENSP00000367952.3		Q8WVF2
UCMA	ENST00000463405.2 link	c.236T>C	p.Val79Ala	missense_variant	Exon 3 of 4	5		ENSP00000473368.1		R4GMV7

Frequencies

GnomAD3 genomes

AF:

0.00343

AC:

521

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.000867

AC:

218

AN:

251400

AF XY:

0.000684

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000351

AC:

513

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000307

AC XY:

223

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.0123

AC:

412

AN:

33474

American (AMR)

AF:

0.000537

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111980

Other (OTH)

AF:

0.000960

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00342

AC:

520

AN:

152150

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0117

AC:

485

AN:

41534

American (AMR)

AF:

0.00170

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00145

Hom.:

Bravo

AF:

0.00431

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00101

AC:

123

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

PhyloP100

1.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.048

Sift

Benign

0.27

T;.

Sift4G

Benign

0.32

T;T

Polyphen

0.34

B;.

Vest4

0.27

MVP

0.16

MPC

0.085

ClinPred

0.016

GERP RS

2.9

Varity_R

0.13

gMVP

0.32

Mutation Taster

=96/4

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

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

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