10-13229614-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145314.3(UCMA):​c.316G>A​(p.Asp106Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: UCMA NM_145314.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.786
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044790268).

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>A	p.Asp106Asn	missense	Exon 4 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_001303118.2		c.220G>A	p.Asp74Asn	missense	Exon 3 of 4	NP_001290047.1
	UCMA	NM_001303119.2		c.154G>A	p.Asp52Asn	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>A	p.Asp106Asn	missense	Exon 4 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000463405.2	TSL:5	c.250G>A	p.Asp84Asn	missense	Exon 3 of 4	ENSP00000473368.1	R4GMV7
	UCMA	ENST00000914827.1		c.220G>A	p.Asp74Asn	missense	Exon 3 of 4	ENSP00000584886.1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152180 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000215 AC: 54 AN: 251194 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000101 AC: 147 AN: 1461462 Hom.: 0 Cov.: 30 AF XY: 0.000124 AC XY: 90 AN XY: 727040

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.0000447 AC: 2 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

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

South Asian (SAS) AF: 0.000615 AC: 53 AN: 86208

European-Finnish (FIN) AF: 0.000636 AC: 34 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111710

Other (OTH) AF: 0.000116 AC: 7 AN: 60378

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152180 Hom.: 0 Cov.: 31 AF XY: 0.000363 AC XY: 27 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68038

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00158 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.000214 AC: 26

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.79
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.091
Sift	Benign	0.13	T
Sift4G	Benign	0.22	T
Polyphen		0.74	P
Vest4		0.32
MutPred		0.11		Gain of helix (P = 0.1736)
MVP		0.16
MPC		0.33
ClinPred		0.072	T
GERP RS		3.4
Varity_R		0.26
gMVP		0.38
Mutation Taster		=83/17	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; COSMIC: COSV66321505;