rs371703029

Variant names:

• chr17-5133536-C-A
• rs371703029
• NM_001304284.2:c.370C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-5133536-C-A
• chr17-5133536-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304284.2(USP6):​c.370C>A​(p.Pro124Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP6 NM_001304284.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

Genes affected

USP6 (HGNC:12629): (ubiquitin specific peptidase 6) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination and regulation of vesicle-mediated transport. Located in plasma membrane and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114955336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP6	NM_001304284.2	c.370C>A	p.Pro124Thr	missense_variant	Exon 14 of 38	ENST00000574788.6	NP_001291213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP6	ENST00000574788.6	c.370C>A	p.Pro124Thr	missense_variant	Exon 14 of 38	1	NM_001304284.2	ENSP00000460380.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250446 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135666

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1458904 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725756

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.0	.;D
REVEL	Benign	0.087
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.53	P;P
Vest4		0.14
MutPred		0.47		Gain of MoRF binding (P = 0.0536);Gain of MoRF binding (P = 0.0536);
MVP		0.32
MPC		0.82
ClinPred		0.82	D
GERP RS		-1.7
Varity_R		0.31
gMVP		0.31

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: rs371703029; hg19: chr17-5036831;