rs10493008

Variant names:

• chr1-21687278-G-A
• rs10493008
• NM_032236.8:c.3010-39C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-21687278-G-A
• chr1-21687278-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032236.8(USP48):​c.3010-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,592,588 control chromosomes in the GnomAD database, including 171,615 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.44 (15316 hom., cov: 32)
  • Exomes 𝑓: 0.46 (156299 hom.)
• Consequence: USP48 NM_032236.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 21 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: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP48	NM_032236.8	MANE Select	c.3010-39C>T		intron	N/A	NP_115612.4
	USP48	NM_001350167.2		c.3007-39C>T		intron	N/A	NP_001337096.1
	USP48	NM_001350168.2		c.3007-39C>T		intron	N/A	NP_001337097.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP48	ENST00000308271.14	TSL:1 MANE Select	c.3010-39C>T		intron	N/A	ENSP00000309262.9
	USP48	ENST00000529637.5	TSL:1	c.3046-39C>T		intron	N/A	ENSP00000431949.1
	USP48	ENST00000400301.5	TSL:1	c.2854-39C>T		intron	N/A	ENSP00000383157.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66791 AN: 151950 Hom.: 15307 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.457

GnomAD2 exomes AF: 0.499 AC: 114052 AN: 228358 AF XY: 0.489

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.669

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.461 AC: 664045 AN: 1440520 Hom.: 156299 Cov.: 28 AF XY: 0.460 AC XY: 329149 AN XY: 716034

African (AFR) AF: 0.344 AC: 11327 AN: 32886

American (AMR) AF: 0.719 AC: 31154 AN: 43338

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 10684 AN: 25810

East Asian (EAS) AF: 0.651 AC: 25431 AN: 39082

South Asian (SAS) AF: 0.453 AC: 37946 AN: 83852

European-Finnish (FIN) AF: 0.403 AC: 21177 AN: 52584

Middle Eastern (MID) AF: 0.387 AC: 2218 AN: 5724

European-Non Finnish (NFE) AF: 0.453 AC: 497058 AN: 1097650

Other (OTH) AF: 0.454 AC: 27050 AN: 59594

GnomAD4 genome AF: 0.439 AC: 66813 AN: 152068 Hom.: 15316 Cov.: 32 AF XY: 0.444 AC XY: 32973 AN XY: 74334

African (AFR) AF: 0.349 AC: 14483 AN: 41472

American (AMR) AF: 0.608 AC: 9284 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3472

East Asian (EAS) AF: 0.657 AC: 3394 AN: 5168

South Asian (SAS) AF: 0.448 AC: 2157 AN: 4814

European-Finnish (FIN) AF: 0.388 AC: 4101 AN: 10572

Middle Eastern (MID) AF: 0.396 AC: 114 AN: 288

European-Non Finnish (NFE) AF: 0.448 AC: 30462 AN: 67976

Other (OTH) AF: 0.454 AC: 959 AN: 2114

Alfa AF: 0.448 Hom.: 44566

Bravo AF: 0.454

Asia WGS AF: 0.522 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.35
PhyloP100		-1.1
BranchPoint Hunter		0.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs10493008; hg19: chr1-22013771;