chr7-6112051-A-C

Position:

• chr7-6112051-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP42	NM_032172.3	c.241+677A>C		intron_variant		ENST00000306177.10	NP_115548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP42	ENST00000306177.10	c.241+677A>C		intron_variant		5	NM_032172.3	ENSP00000301962	P1

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

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.0308

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.0919

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.0640

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs12667392; hg19: chr7-6151682;