rs80070283

Variant names:

• chr10-13229628-A-G
• rs80070283
• NM_145314.3:c.302T>C

Variant summary

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

The NM_145314.3(UCMA):​c.302T>C​(p.Val101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,613,968 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0034 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (5 hom.)
• Consequence: UCMA NM_145314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 1 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=0.006891668).
• BS2: High Homozygotes in GnomAd4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	NM_145314.3	MANE Select	c.302T>C	p.Val101Ala	missense	Exon 4 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_001303118.2		c.206T>C	p.Val69Ala	missense	Exon 3 of 4	NP_001290047.1
	UCMA	NM_001303119.2		c.140T>C	p.Val47Ala	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.302T>C	p.Val101Ala	missense	Exon 4 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000463405.2	TSL:5	c.236T>C	p.Val79Ala	missense	Exon 3 of 4	ENSP00000473368.1	R4GMV7
	UCMA	ENST00000914827.1		c.206T>C	p.Val69Ala	missense	Exon 3 of 4	ENSP00000584886.1

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 521 AN: 152034 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000867 AC: 218 AN: 251400 AF XY: 0.000684

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000351 AC: 513 AN: 1461818 Hom.: 5 Cov.: 31 AF XY: 0.000307 AC XY: 223 AN XY: 727214

African (AFR) AF: 0.0123 AC: 412 AN: 33474

American (AMR) AF: 0.000537 AC: 24 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111980

Other (OTH) AF: 0.000960 AC: 58 AN: 60390

GnomAD4 genome AF: 0.00342 AC: 520 AN: 152150 Hom.: 5 Cov.: 31 AF XY: 0.00332 AC XY: 247 AN XY: 74388

African (AFR) AF: 0.0117 AC: 485 AN: 41534

American (AMR) AF: 0.00170 AC: 26 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.00431

ESP6500AA AF: 0.00885 AC: 39

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00101 AC: 123

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.048
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.34	B
Vest4		0.27
MVP		0.16
MPC		0.085
ClinPred		0.016	T
GERP RS		2.9
Varity_R		0.13
gMVP		0.32
Mutation Taster		=96/4	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: rs80070283; hg19: chr10-13271628; COSMIC: COSV99059960;