chr16-23068386-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020718.4(USP31):​c.3719G>A​(p.Arg1240His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

USP31
NM_020718.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2722262).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
USP31NM_020718.4 linkuse as main transcriptc.3719G>A p.Arg1240His missense_variant 16/16 ENST00000219689.12 NP_065769.3 Q70CQ4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USP31ENST00000219689.12 linkuse as main transcriptc.3719G>A p.Arg1240His missense_variant 16/161 NM_020718.4 ENSP00000219689.7 Q70CQ4-1
USP31ENST00000567975.1 linkuse as main transcriptc.1598G>A p.Arg533His missense_variant 2/22 ENSP00000461621.1 I3L4X5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461700
Hom.:
0
Cov.:
40
AF XY:
0.00000275
AC XY:
2
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 11, 2023The c.3719G>A (p.R1240H) alteration is located in exon 16 (coding exon 16) of the USP31 gene. This alteration results from a G to A substitution at nucleotide position 3719, causing the arginine (R) at amino acid position 1240 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.030
T;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.21
Sift
Uncertain
0.0020
D;.
Sift4G
Uncertain
0.0070
D;D
Polyphen
1.0
D;.
Vest4
0.26
MutPred
0.24
Loss of MoRF binding (P = 0.0602);.;
MVP
0.78
MPC
0.95
ClinPred
0.91
D
GERP RS
5.5
Varity_R
0.13
gMVP
0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23079707; COSMIC: COSV54851999; COSMIC: COSV54851999; API