rs6497650

chr16-23121072-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020718.4(USP31):c.634-12889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,098 control chromosomes in the GnomAD database, including 6,315 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 0.28 (6315 hom., cov: 32)
• Consequence: USP31 NM_020718.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

USP31 (HGNC:20060): (ubiquitin specific peptidase 31) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination. Located in 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP31	NM_020718.4	c.634-12889G>A		intron_variant		ENST00000219689.12
USP31	NM_001387221.1	c.634-12889G>A		intron_variant
USP31	XM_047434389.1	c.634-12889G>A		intron_variant
USP31	NR_170599.1	n.816-12889G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP31	ENST00000219689.12	c.634-12889G>A		intron_variant		1	NM_020718.4	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42547 AN: 151980 Hom.: 6294 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42622 AN: 152098 Hom.: 6315 Cov.: 32 AF XY: 0.281 AC XY: 20861 AN XY: 74346

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.280

Alfa AF: 0.303 Hom.: 1421

Bravo AF: 0.279

Asia WGS AF: 0.281 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.076
Dann	Benign	0.59

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: rs6497650; hg19: chr16-23132393;