NM_020718.4:c.634-12889G>A

Variant names:

• chr16-23121072-C-T
• rs6497650
• NM_020718.4:c.634-12889G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USP31	NM_020718.4	c.634-12889G>A		intron_variant	Intron 1 of 15	ENST00000219689.12	NP_065769.3
USP31	NM_001387221.1	c.634-12889G>A		intron_variant	Intron 1 of 14		NP_001374150.1
USP31	NR_170599.1	n.816-12889G>A		intron_variant	Intron 1 of 15
USP31	XM_047434389.1	c.634-12889G>A		intron_variant	Intron 1 of 13		XP_047290345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP31	ENST00000219689.12	c.634-12889G>A		intron_variant	Intron 1 of 15	1	NM_020718.4	ENSP00000219689.7

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

African (AFR) AF: 0.196 AC: 8149 AN: 41484

American (AMR) AF: 0.350 AC: 5342 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3468

East Asian (EAS) AF: 0.173 AC: 895 AN: 5178

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4816

European-Finnish (FIN) AF: 0.362 AC: 3826 AN: 10568

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 21176 AN: 67990

Other (OTH) AF: 0.280 AC: 592 AN: 2112

Alfa AF: 0.301 Hom.: 1437

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
PhyloP100		-1.7
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: rs6497650; hg19: chr16-23132393;