10-13222280-C-T

Variant names:

• chr10-13222280-C-T
• rs2281797
• NM_145314.3:c.320-80G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145314.3(UCMA):​c.320-80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000843 in 1,186,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: UCMA NM_145314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.320-80G>A		intron	N/A	NP_660357.2
	UCMA	NM_001303118.2		c.224-80G>A		intron	N/A	NP_001290047.1
	UCMA	NM_001303119.2		c.158-80G>A		intron	N/A	NP_001290048.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.320-80G>A		intron	N/A	ENSP00000367952.3
	UCMA	ENST00000463405.2	TSL:5	c.254-80G>A		intron	N/A	ENSP00000473368.1
	UCMA	ENST00000914827.1		c.224-80G>A		intron	N/A	ENSP00000584886.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.43e-7 AC: 1 AN: 1186612 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 596276

African (AFR) AF: 0.00 AC: 0 AN: 28594

American (AMR) AF: 0.00 AC: 0 AN: 35974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22876

East Asian (EAS) AF: 0.00 AC: 0 AN: 37300

South Asian (SAS) AF: 0.00 AC: 0 AN: 74476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4854

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 885378

Other (OTH) AF: 0.00 AC: 0 AN: 51304

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.60
PhyloP100		-1.4

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: rs2281797; hg19: chr10-13264280;