10-13233742-C-T

Variant names:

• chr10-13233742-C-T
• rs376911016
• NM_145314.3:c.117G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_145314.3(UCMA):​c.117G>A​(p.Ala39Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,614,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: UCMA NM_145314.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-13233742-C-T is Benign according to our data. Variant chr10-13233742-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3185951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCMA	NM_145314.3	c.117G>A	p.Ala39Ala	synonymous_variant	Exon 2 of 5	ENST00000378681.8	NP_660357.2
UCMA	NM_001303118.2	c.117G>A	p.Ala39Ala	synonymous_variant	Exon 2 of 4		NP_001290047.1
UCMA	NM_001303119.2	c.58+459G>A		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.117G>A	p.Ala39Ala	synonymous_variant	Exon 2 of 5	1	NM_145314.3	ENSP00000367952.3
UCMA	ENST00000463405.2	c.59-109G>A		intron_variant	Intron 1 of 3	5		ENSP00000473368.1

Frequencies

GnomAD3 genomes AF: 0.000395 AC: 60 AN: 152050 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000207 AC: 52 AN: 251410 Hom.: 0 AF XY: 0.000140 AC XY: 19 AN XY: 135880

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000162 AC: 237 AN: 1461872 Hom.: 1 Cov.: 34 AF XY: 0.000171 AC XY: 124 AN XY: 727240

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152168 Hom.: 0 Cov.: 31 AF XY: 0.000296 AC XY: 22 AN XY: 74400

Gnomad4 AFR AF: 0.000723

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000393

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.8
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs376911016; hg19: chr10-13275742;