NM_145314.3:c.17_220+223del

Variant names:

• chr10-13233314-TGGGGCCTCCTAACCCTGACAAAGTATTCAATCCAATATACGACCTACAGTCAGGAAATAGGGTGTAATTTCTCATTCAGAGCTGCAGTCCCTTTGATACCCTGGGGTGAGCCCTTCGTGCCCAGCTGCATCCTGCTGCCCGGCTGACTGTGGGAGAGGAGGAGCCGGGGGGTGTGAGCAGAGGTGGTGATGGACGCGGGATGGGGTCCCTCCAGCATCCTTACCATTGACCTCATCTCTGGACTTGGGGGACCGCTTGCCGCGCCTCTTGAGGAAATTCGAGGCATCTGATTCCTGCATGAAAATCTTCTGTTTTGCATCTGAAACCCGGGAGAGGCCTGTCACCAGCAGTGTGGGGGTGCTGGGGCTGCTGCTTCGCTGGCTGCACCTGCCCTGCCCCGTGGGTGGCCCCTGCACTCACCTTCACTCGCCTCTTCTCCCGCCATCTGCATGGTGCCCACAGATACACTGGTTCCCTCTCTCAGCACTGCAGGACAAGGGCACAGAGTGAGGCTGCAGCATCAGAGGGGAGCCCAGACCCTGAGCTGAGTCCCCATCTCTCTTTCCAGGCTAAGCGTCCTGCCAGGGCCTGGCAGGGGGCCCGTGGTTTCTCACGTACCAGCTGCAGAGCCAATCTCCCCAGGAACCCACCAAGCAAGCTGGCTTGGGTTTTTTTTCTATTTTGTTTCTTTCTTTACTGTTTTTTATTATTATTATTATTTTTCTGTATTGCATTGTGTCCTACATGCACACGACACACACATACACACATGTTAACAATAAGCATACTCCTTTCTACCTGCATCACCTGAGCAGCCTTACCTGTGCATGGTAAGTCTCCCTTACCATGTAACTAACACCCTCCACCTTGACCCTCCTGTACTCACTAGACAGGAGCACCACGGCGGAGAAGCAAGACAGCAGGACGG-T
• rs2131608474
• NM_145314.3:c.17_220+223del

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_145314.3(UCMA):​c.17_220+223del​(p.Ala6_Asn73del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UCMA NM_145314.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.915
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_145314.3.

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.17_220+223del	p.Ala6_Asn73del	conservative_inframe_deletion	Exon 1 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_145314.3	MANE Select	c.17_220+223del		exon_loss	Exon 2 of 5	NP_660357.2	Q8WVF2
	UCMA	NM_145314.3	MANE Select	c.17_220+223del		exon_loss	Exon 3 of 5	NP_660357.2	Q8WVF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.17_220+223del	p.Ala6_Asn73del	conservative_inframe_deletion	Exon 3 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.17_220+223del		exon_loss	Exon 3 of 5	ENSP00000367952.3	Q8WVF2
	UCMA	ENST00000378681.8	TSL:1 MANE Select	c.17_220+223del		exon_loss	Exon 2 of 5	ENSP00000367952.3	Q8WVF2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.92

Splicing

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

Other links and lift over

dbSNP: rs2131608474; hg19: chr10-13275314;