10-13222280-C-A

Position:

• chr10-13222280-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCMA	NM_145314.3	c.320-80G>T		intron_variant		ENST00000378681.8
UCMA	NM_001303118.2	c.224-80G>T		intron_variant
UCMA	NM_001303119.2	c.158-80G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCMA	ENST00000378681.8	c.320-80G>T		intron_variant		1	NM_145314.3	P1
UCMA	ENST00000463405.2	c.254-80G>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.443

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.283

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.296

Alfa AF: 0.269 Hom.: 6933

Bravo AF: 0.305

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281797; hg19: chr10-13264280;