10-13233764-A-C

Variant names:

• chr10-13233764-A-C
• rs41291317
• NM_145314.3:c.95T>G
• UCMA p.Met32Arg

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145314.3(UCMA):​c.95T>G​(p.Met32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M32T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UCMA NM_145314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036997646).

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.95T>G	p.Met32Arg	missense	Exon 2 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_001303118.2		c.95T>G	p.Met32Arg	missense	Exon 2 of 4	NP_001290047.1
	UCMA	NM_001303119.2		c.58+437T>G		intron	N/A	NP_001290048.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.95T>G	p.Met32Arg	missense	Exon 2 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000914827.1		c.95T>G	p.Met32Arg	missense	Exon 2 of 4	ENSP00000584886.1
	UCMA	ENST00000463405.2	TSL:5	c.59-131T>G		intron	N/A	ENSP00000473368.1	R4GMV7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.038
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.041
DANN	Benign	0.16
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.9	N
PhyloP100		-0.30
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.010
Sift	Benign	0.62	T
Sift4G	Benign	0.57	T
Varity_R		0.23
gMVP		0.078
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41291317;

hg19: chr10-13275764;