Variant chr10-13233632-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145314.3(UCMA):c.126T>G(p.Asp42Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UCMA
NM_145314.3 missense, splice_region

Scores

Splicing: ADA: 0.0004633

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04410371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UCMA	NM_145314.3 linkuse as main transcript	c.126T>G	p.Asp42Glu	missense_variant, splice_region_variant	3/5	ENST00000378681.8
UCMA	NM_001303118.2 linkuse as main transcript	c.124+103T>G		intron_variant
UCMA	NM_001303119.2 linkuse as main transcript	c.58+569T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCMA	ENST00000378681.8 linkuse as main transcript	c.126T>G	p.Asp42Glu	missense_variant, splice_region_variant	3/5	1	NM_145314.3	P1
UCMA	ENST00000463405.2 linkuse as main transcript	c.60T>G	p.Asn20Lys	missense_variant, splice_region_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251432

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000137

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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

Cov.:

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

Sep 15, 2021

The c.126T>G (p.D42E) alteration is located in exon 3 (coding exon 3) of the UCMA gene. This alteration results from a T to G substitution at nucleotide position 126, causing the aspartic acid (D) at amino acid position 42 to be replaced by a glutamic acid (E). 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

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.017

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.39

M_CAP

Benign

0.0020

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

REVEL

Benign

0.042

Sift

Benign

0.044

Sift4G

Benign

0.074

Polyphen

0.14

Vest4

0.083

MutPred

0.13

Gain of helix (P = 0.0425);

MVP

0.030

MPC

0.085

ClinPred

0.068

GERP RS

0.34

Varity_R

0.056

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00046

dbscSNV1_RF

Benign

0.068

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: 1

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