Genetic Variant UCMA:p.Val101Met (chr10-13229629-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_145314.3(UCMA):c.301G>A(p.Val101Met) variant causes a missense change. The variant allele was found at a frequency of 0.000414 in 1,614,100 control chromosomes in the GnomAD database, including 3 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 0.0023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 3 hom. )

Consequence

UCMA
NM_145314.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.86

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=0.0079374015).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCMA	NM_145314.3 link	c.301G>A	p.Val101Met	missense_variant	Exon 4 of 5	ENST00000378681.8	NP_660357.2	Q8WVF2A0A067XJX6
UCMA	NM_001303118.2 link	c.205G>A	p.Val69Met	missense_variant	Exon 3 of 4		NP_001290047.1	Q8WVF2A0A067XJP8
UCMA	NM_001303119.2 link	c.139G>A	p.Val47Met	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.301G>A	p.Val101Met	missense_variant	Exon 4 of 5	1	NM_145314.3	ENSP00000367952.3		Q8WVF2
UCMA	ENST00000463405.2 link	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 4	5		ENSP00000473368.1		R4GMV7

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000577

AC:

145

AN:

251378

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000217

AC:

317

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

129

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00786

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152280

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00811

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00258

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000684

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.10

Sift

Uncertain

0.014

D;.

Sift4G

Uncertain

0.021

D;D

Polyphen

1.0

D;.

Vest4

0.45

MVP

0.30

MPC

0.35

ClinPred

0.033

GERP RS

5.2

Varity_R

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over