NM_145314.3:c.320-80G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145314.3(UCMA):​c.320-80G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,336,252 control chromosomes in the GnomAD database, including 55,542 homozygotes. 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: 𝑓 0.30 (7277 hom., cov: 31)
  • Exomes 𝑓: 0.27 (48265 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	NM_145314.3	MANE Select	c.320-80G>T		intron	N/A	NP_660357.2
	UCMA	NM_001303118.2		c.224-80G>T		intron	N/A	NP_001290047.1
	UCMA	NM_001303119.2		c.158-80G>T		intron	N/A	NP_001290048.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45154 AN: 151974 Hom.: 7258 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.272 AC: 322502 AN: 1184160 Hom.: 48265 AF XY: 0.275 AC XY: 163648 AN XY: 595032

African (AFR) AF: 0.287 AC: 8183 AN: 28548

American (AMR) AF: 0.443 AC: 15929 AN: 35940

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 5967 AN: 22860

East Asian (EAS) AF: 0.592 AC: 22065 AN: 37268

South Asian (SAS) AF: 0.354 AC: 26353 AN: 74370

European-Finnish (FIN) AF: 0.282 AC: 12914 AN: 45790

Middle Eastern (MID) AF: 0.307 AC: 1489 AN: 4848

European-Non Finnish (NFE) AF: 0.244 AC: 215108 AN: 883330

Other (OTH) AF: 0.283 AC: 14494 AN: 51206

GnomAD4 genome AF: 0.297 AC: 45212 AN: 152092 Hom.: 7277 Cov.: 31 AF XY: 0.305 AC XY: 22649 AN XY: 74350

African (AFR) AF: 0.289 AC: 11970 AN: 41482

American (AMR) AF: 0.398 AC: 6073 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3097 AN: 5166

South Asian (SAS) AF: 0.371 AC: 1790 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2979 AN: 10582

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17422 AN: 67986

Other (OTH) AF: 0.296 AC: 622 AN: 2102

Alfa AF: 0.271 Hom.: 9125

Bravo AF: 0.305

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.69
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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;