rs756021993

Variant names:

• chr10-13222182-C-G
• rs756021993
• NM_145314.3:c.338G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-13222182-C-G
• chr10-13222182-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145314.3(UCMA):​c.338G>C​(p.Arg113Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R113W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UCMA NM_145314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	NM_145314.3	MANE Select	c.338G>C	p.Arg113Pro	missense	Exon 5 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_001303118.2		c.242G>C	p.Arg81Pro	missense	Exon 4 of 4	NP_001290047.1
	UCMA	NM_001303119.2		c.176G>C	p.Arg59Pro	missense	Exon 3 of 3	NP_001290048.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.338G>C	p.Arg113Pro	missense	Exon 5 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000463405.2	TSL:5	c.272G>C	p.Arg91Pro	missense	Exon 4 of 4	ENSP00000473368.1	R4GMV7
	UCMA	ENST00000914827.1		c.242G>C	p.Arg81Pro	missense	Exon 4 of 4	ENSP00000584886.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.7
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.34		Loss of helix (P = 3e-04)
MVP		0.32
MPC		0.44
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.96
gMVP		0.65
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs756021993; hg19: chr10-13264182;