10-13233553-T-G

Variant names:

• chr10-13233553-T-G
• rs3829925
• NM_145314.3:c.205A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145314.3(UCMA):​c.205A>C​(p.Arg69Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,613,718 control chromosomes in the GnomAD database, including 644,423 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 0.86 (56974 hom., cov: 31)
  • Exomes 𝑓: 0.90 (587449 hom.)
• Consequence: UCMA NM_145314.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 20 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCMA	NM_145314.3	c.205A>C	p.Arg69Arg	synonymous_variant	Exon 3 of 5	ENST00000378681.8	NP_660357.2
UCMA	NM_001303118.2	c.124+182A>C		intron_variant	Intron 2 of 3		NP_001290047.1
UCMA	NM_001303119.2	c.58+648A>C		intron_variant	Intron 1 of 2		NP_001290048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCMA	ENST00000378681.8	c.205A>C	p.Arg69Arg	synonymous_variant	Exon 3 of 5	1	NM_145314.3	ENSP00000367952.3
UCMA	ENST00000463405.2	c.139A>C	p.Arg47Arg	synonymous_variant	Exon 2 of 4	5		ENSP00000473368.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 130995 AN: 151866 Hom.: 56921 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.868

GnomAD2 exomes AF: 0.876 AC: 220137 AN: 251370 AF XY: 0.871

Gnomad AFR exome AF: 0.766

Gnomad AMR exome AF: 0.926

Gnomad ASJ exome AF: 0.877

Gnomad EAS exome AF: 0.823

Gnomad FIN exome AF: 0.894

Gnomad NFE exome AF: 0.912

Gnomad OTH exome AF: 0.885

GnomAD4 exome AF: 0.895 AC: 1308506 AN: 1461734 Hom.: 587449 Cov.: 48 AF XY: 0.891 AC XY: 648163 AN XY: 727160

African (AFR) AF: 0.768 AC: 25697 AN: 33476

American (AMR) AF: 0.923 AC: 41278 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 22966 AN: 26134

East Asian (EAS) AF: 0.841 AC: 33368 AN: 39700

South Asian (SAS) AF: 0.762 AC: 65675 AN: 86230

European-Finnish (FIN) AF: 0.897 AC: 47911 AN: 53418

Middle Eastern (MID) AF: 0.861 AC: 4967 AN: 5766

European-Non Finnish (NFE) AF: 0.911 AC: 1013206 AN: 1111904

Other (OTH) AF: 0.885 AC: 53438 AN: 60390

GnomAD4 genome AF: 0.863 AC: 131106 AN: 151984 Hom.: 56974 Cov.: 31 AF XY: 0.860 AC XY: 63902 AN XY: 74280

African (AFR) AF: 0.771 AC: 31915 AN: 41402

American (AMR) AF: 0.905 AC: 13810 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3040 AN: 3466

East Asian (EAS) AF: 0.828 AC: 4268 AN: 5156

South Asian (SAS) AF: 0.750 AC: 3612 AN: 4818

European-Finnish (FIN) AF: 0.897 AC: 9479 AN: 10570

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.914 AC: 62120 AN: 67990

Other (OTH) AF: 0.868 AC: 1834 AN: 2112

Alfa AF: 0.899 Hom.: 202263

Bravo AF: 0.861

Asia WGS AF: 0.789 AC: 2744 AN: 3478

EpiCase AF: 0.908

EpiControl AF: 0.901

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.36
PhyloP100		1.1
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: rs3829925; hg19: chr10-13275553; COSMIC: COSV66321857;