rs10917042

Variant names:

• chr1-21782877-G-A
• rs10917042
• NM_032236.8:c.81C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-21782877-G-A
• chr1-21782877-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032236.8(USP48):​c.81C>T​(p.His27His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,558,190 control chromosomes in the GnomAD database, including 56,734 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.

• Frequency:
  • Genomes: 𝑓 0.23 (5356 hom., cov: 34)
  • Exomes 𝑓: 0.25 (51378 hom.)
• Consequence: USP48 NM_032236.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=1.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP48	NM_032236.8	c.81C>T	p.His27His	synonymous_variant	Exon 1 of 27	ENST00000308271.14	NP_115612.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP48	ENST00000308271.14	c.81C>T	p.His27His	synonymous_variant	Exon 1 of 27	1	NM_032236.8	ENSP00000309262.9

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34364 AN: 152106 Hom.: 5348 Cov.: 34

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.242

GnomAD2 exomes AF: 0.321 AC: 51029 AN: 158994 AF XY: 0.309

Gnomad AFR exome AF: 0.0563

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.626

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.254 AC: 357124 AN: 1405968 Hom.: 51378 Cov.: 33 AF XY: 0.254 AC XY: 176225 AN XY: 694772

African (AFR) AF: 0.0538 AC: 1694 AN: 31468

American (AMR) AF: 0.589 AC: 21748 AN: 36914

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 4918 AN: 25150

East Asian (EAS) AF: 0.582 AC: 21014 AN: 36076

South Asian (SAS) AF: 0.247 AC: 19669 AN: 79650

European-Finnish (FIN) AF: 0.237 AC: 11523 AN: 48616

Middle Eastern (MID) AF: 0.219 AC: 1133 AN: 5180

European-Non Finnish (NFE) AF: 0.241 AC: 260897 AN: 1084702

Other (OTH) AF: 0.250 AC: 14528 AN: 58212

GnomAD4 genome AF: 0.226 AC: 34378 AN: 152222 Hom.: 5356 Cov.: 34 AF XY: 0.233 AC XY: 17363 AN XY: 74408

African (AFR) AF: 0.0647 AC: 2691 AN: 41576

American (AMR) AF: 0.448 AC: 6851 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3130 AN: 5154

South Asian (SAS) AF: 0.237 AC: 1145 AN: 4830

European-Finnish (FIN) AF: 0.232 AC: 2459 AN: 10596

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16563 AN: 67984

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.247 Hom.: 8901

Bravo AF: 0.238

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		2.0
PromoterAI		0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
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: rs10917042; hg19: chr1-22109370; COSMIC: COSV57612926; COSMIC: COSV57612926;