rs760151703

Variant names:

• chr10-13229614-C-A
• rs760151703
• NM_145314.3:c.316G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-13229614-C-A
• chr10-13229614-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.316G>T​(p.Asp106Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D106N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UCMA NM_145314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• 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.316G>T	p.Asp106Tyr	missense	Exon 4 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_001303118.2		c.220G>T	p.Asp74Tyr	missense	Exon 3 of 4	NP_001290047.1
	UCMA	NM_001303119.2		c.154G>T	p.Asp52Tyr	missense	Exon 2 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.316G>T	p.Asp106Tyr	missense	Exon 4 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000463405.2	TSL:5	c.250G>T	p.Asp84Tyr	missense	Exon 3 of 4	ENSP00000473368.1	R4GMV7
	UCMA	ENST00000914827.1		c.220G>T	p.Asp74Tyr	missense	Exon 3 of 4	ENSP00000584886.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461462 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727040

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111710

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.051
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.79
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.15		Gain of phosphorylation at D106 (P = 0.0203)
MVP		0.19
MPC		0.40
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.70
gMVP		0.54
Mutation Taster		=75/25	polymorphism

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: rs760151703; hg19: chr10-13271614;