NM_032236.8:c.1900_1902delTCAinsACC

Variant names:

• chr1-21715450-TGA-GGT
• NM_032236.8:c.1900_1902delTCAinsACC
• USP48 p.Ser634Thr

Variant summary

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

The NM_032236.8(USP48):​c.1900_1902delTCAinsACC​(p.Ser634Thr) variant causes a missense change. 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP48 NM_032236.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69
• Publications: 0 publications found

Genes affected

USP48 (HGNC:18533): (ubiquitin specific peptidase 48) This gene encodes a protein containing domains that associate it with the peptidase family C19, also known as family 2 of ubiquitin carboxyl-terminal hydrolases. Family members function as deubiquitinating enzymes, recognizing and hydrolyzing the peptide bond at the C-terminal glycine of ubiquitin. Enzymes in peptidase family C19 are involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

USP48 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 85

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032236.8. 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
	USP48	NM_032236.8	MANE Select	c.1900_1902delTCAinsACC	p.Ser634Thr	missense	N/A	NP_115612.4	Q86UV5-1
	USP48	NM_001350167.2		c.1897_1899delTCAinsACC	p.Ser633Thr	missense	N/A	NP_001337096.1
	USP48	NM_001350168.2		c.1897_1899delTCAinsACC	p.Ser633Thr	missense	N/A	NP_001337097.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP48	ENST00000308271.14	TSL:1 MANE Select	c.1900_1902delTCAinsACC	p.Ser634Thr	missense	N/A	ENSP00000309262.9	Q86UV5-1
	USP48	ENST00000529637.5	TSL:1	c.1897_1899delTCAinsACC	p.Ser633Thr	missense	N/A	ENSP00000431949.1	Q86UV5-8
	USP48	ENST00000400301.5	TSL:1	c.1900_1902delTCAinsACC	p.Ser634Thr	missense	N/A	ENSP00000383157.1	Q86UV5-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

Splicing

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

hg19: chr1-22041943;