10-13222200-T-C

Position:

chr10-13222200-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145314.3(UCMA):c.320A>G(p.Glu107Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000105 in 1,613,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

UCMA
NM_145314.3 missense, splice_region

Scores

Splicing: ADA: 0.6159

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25464737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCMA	NM_145314.3 linkuse as main transcript	c.320A>G	p.Glu107Gly	missense_variant, splice_region_variant	5/5	ENST00000378681.8	NP_660357.2	Q8WVF2A0A067XJX6
UCMA	NM_001303118.2 linkuse as main transcript	c.224A>G	p.Glu75Gly	missense_variant, splice_region_variant	4/4		NP_001290047.1	Q8WVF2A0A067XJP8
UCMA	NM_001303119.2 linkuse as main transcript	c.158A>G	p.Glu53Gly	missense_variant, splice_region_variant	3/3		NP_001290048.1	Q8WVF2A0A067XKV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCMA	ENST00000378681.8 linkuse as main transcript	c.320A>G	p.Glu107Gly	missense_variant, splice_region_variant	5/5	1	NM_145314.3	ENSP00000367952.3		Q8WVF2
UCMA	ENST00000463405.2 linkuse as main transcript	c.254A>G	p.Glu85Gly	missense_variant, splice_region_variant	4/4	5		ENSP00000473368.1		R4GMV7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249246

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.320A>G (p.E107G) alteration is located in exon 5 (coding exon 5) of the UCMA gene. This alteration results from a A to G substitution at nucleotide position 320, causing the glutamic acid (E) at amino acid position 107 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.25

T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.6

D;.

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.53

MutPred

0.13

Gain of loop (P = 0.0097);.;

MVP

0.25

MPC

0.40

ClinPred

0.90

GERP RS

5.2

Varity_R

0.82

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.62

dbscSNV1_RF

Benign

0.70

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