16-23068594-T-G

Variant names:

• chr16-23068594-T-G
• rs765986233
• NM_020718.4:c.3511A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020718.4(USP31):​c.3511A>C​(p.Thr1171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1171A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP31 NM_020718.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11848959).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020718.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP31	NM_020718.4	MANE Select	c.3511A>C	p.Thr1171Pro	missense	Exon 16 of 16	NP_065769.3
	USP31	NM_001387221.1		c.3391A>C	p.Thr1131Pro	missense	Exon 15 of 15	NP_001374150.1
	USP31	NR_170599.1		n.3804A>C		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP31	ENST00000219689.12	TSL:1 MANE Select	c.3511A>C	p.Thr1171Pro	missense	Exon 16 of 16	ENSP00000219689.7	Q70CQ4-1
	USP31	ENST00000953487.1		c.3391A>C	p.Thr1131Pro	missense	Exon 15 of 15	ENSP00000623546.1
	USP31	ENST00000567975.1	TSL:2	c.1390A>C	p.Thr464Pro	missense	Exon 2 of 2	ENSP00000461621.1	I3L4X5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.49
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.039
Sift	Benign	0.071	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.18		Loss of phosphorylation at T1171 (P = 0.0165)
MVP		0.43
MPC		0.30
ClinPred		0.062	T
GERP RS		0.79
Varity_R		0.11
gMVP		0.13

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: rs765986233; hg19: chr16-23079915;