10-13229629-C-T

Variant names:

• chr10-13229629-C-T
• rs74123515
• NM_145314.3:c.301G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145314.3(UCMA):​c.301G>A​(p.Val101Met) variant causes a missense change. The variant allele was found at a frequency of 0.000414 in 1,614,100 control chromosomes in the GnomAD database, including 3 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 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (3 hom.)
• Consequence: UCMA NM_145314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0079374015).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.301G>A	p.Val101Met	missense	Exon 4 of 5	NP_660357.2
	UCMA	NM_001303118.2		c.205G>A	p.Val69Met	missense	Exon 3 of 4	NP_001290047.1
	UCMA	NM_001303119.2		c.139G>A	p.Val47Met	missense	Exon 2 of 3	NP_001290048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.301G>A	p.Val101Met	missense	Exon 4 of 5	ENSP00000367952.3
	UCMA	ENST00000463405.2	TSL:5	c.235G>A	p.Val79Met	missense	Exon 3 of 4	ENSP00000473368.1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000577 AC: 145 AN: 251378 AF XY: 0.000412

Gnomad AFR exome AF: 0.00794

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000217 AC: 317 AN: 1461820 Hom.: 3 Cov.: 31 AF XY: 0.000177 AC XY: 129 AN XY: 727210

African (AFR) AF: 0.00786 AC: 263 AN: 33476

American (AMR) AF: 0.000358 AC: 16 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111978

Other (OTH) AF: 0.000497 AC: 30 AN: 60390

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152280 Hom.: 0 Cov.: 31 AF XY: 0.00218 AC XY: 162 AN XY: 74460

African (AFR) AF: 0.00811 AC: 337 AN: 41576

American (AMR) AF: 0.000589 AC: 9 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00258

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000684 AC: 83

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.45
MVP		0.30
MPC		0.35
ClinPred		0.033	T
GERP RS		5.2
Varity_R		0.22
gMVP		0.41
Mutation Taster		=84/16	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: rs74123515; hg19: chr10-13271629; COSMIC: COSV99059959;