7-6112051-A-C

Variant names:

• chr7-6112051-A-C
• rs12667392
• NM_032172.3:c.241+677A>C

Variant summary

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

The NM_032172.3(USP42):​c.241+677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,250 control chromosomes in the GnomAD database, including 620 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 0.078 (620 hom., cov: 31)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: USP42 NM_032172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 2 publications found

Genes affected

USP42 (HGNC:20068): (ubiquitin specific peptidase 42) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032172.3. 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
	USP42	NM_032172.3	MANE Select	c.241+677A>C		intron	N/A	NP_115548.1
	USP42	NM_001389650.1		c.241+677A>C		intron	N/A	NP_001376579.1
	USP42	NM_001365764.1		c.241+677A>C		intron	N/A	NP_001352693.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP42	ENST00000306177.10	TSL:5 MANE Select	c.241+677A>C		intron	N/A	ENSP00000301962.5
	USP42	ENST00000479544.6	TSL:1	n.308+677A>C		intron	N/A
	USP42	ENST00000465073.6	TSL:5	c.241+677A>C		intron	N/A	ENSP00000430568.1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11930 AN: 152016 Hom.: 621 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0647

GnomAD4 exome AF: 0.0431 AC: 5 AN: 116 Hom.: 0 AF XY: 0.0208 AC XY: 1 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.0400 AC: 4 AN: 100

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0784 AC: 11930 AN: 152134 Hom.: 620 Cov.: 31 AF XY: 0.0794 AC XY: 5902 AN XY: 74368

African (AFR) AF: 0.137 AC: 5676 AN: 41498

American (AMR) AF: 0.0423 AC: 645 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.0308 AC: 160 AN: 5192

South Asian (SAS) AF: 0.0869 AC: 419 AN: 4822

European-Finnish (FIN) AF: 0.0919 AC: 971 AN: 10570

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3756 AN: 68008

Other (OTH) AF: 0.0640 AC: 135 AN: 2108

Alfa AF: 0.0774 Hom.: 103

Bravo AF: 0.0749

Asia WGS AF: 0.0540 AC: 188 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	3.8
DANN	Benign	0.66
PhyloP100		2.0
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: rs12667392; hg19: chr7-6151682;