rs10034164

Variant names:

• chr4-52593565-A-G
• rs10034164
• NM_022832.4:c.*4075T>C

Variant summary

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

The NM_022832.4(USP46):​c.*4075T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,270 control chromosomes in the GnomAD database, including 3,021 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 0.18 (3020 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: USP46 NM_022832.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 6 publications found

Genes affected

USP46 (HGNC:20075): (ubiquitin specific peptidase 46) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022832.4. 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
	USP46	NM_022832.4	MANE Select	c.*4075T>C		3_prime_UTR	Exon 9 of 9	NP_073743.2
	USP46	NM_001134223.2		c.*4075T>C		3_prime_UTR	Exon 9 of 9	NP_001127695.1
	USP46	NM_001286767.2		c.*4075T>C		3_prime_UTR	Exon 9 of 9	NP_001273696.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP46	ENST00000441222.8	TSL:1 MANE Select	c.*4075T>C		3_prime_UTR	Exon 9 of 9	ENSP00000407818.2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27244 AN: 152112 Hom.: 2995 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.125 AC: 5 AN: 40 Hom.: 1 Cov.: 0 AF XY: 0.133 AC XY: 4 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.0588 AC: 2 AN: 34

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.180 AC: 27327 AN: 152230 Hom.: 3020 Cov.: 33 AF XY: 0.178 AC XY: 13274 AN XY: 74434

African (AFR) AF: 0.324 AC: 13462 AN: 41506

American (AMR) AF: 0.140 AC: 2143 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.157 AC: 812 AN: 5178

South Asian (SAS) AF: 0.126 AC: 610 AN: 4830

European-Finnish (FIN) AF: 0.119 AC: 1268 AN: 10620

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8051 AN: 68008

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.160 Hom.: 426

Bravo AF: 0.191

Asia WGS AF: 0.170 AC: 592 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	0.35
DANN	Benign	0.45
PhyloP100		-1.0
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: rs10034164; hg19: chr4-53459731;