chrX-41123708-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001039591.3(USP9X):​c.80C>T​(p.Pro27Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,465 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts 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. P27H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

USP9X
NM_001039591.3 missense

Scores

2
4
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
USP9X (HGNC:12632): (ubiquitin specific peptidase 9 X-linked) This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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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;
PP2
Missense variant in the USP9X gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 24 curated pathogenic missense variants (we use a threshold of 10). The gene has 36 curated benign missense variants. Gene score misZ: 6.4105 (above the threshold of 3.09). GenCC associations: The gene is linked to non-syndromic X-linked intellectual disability, X-linked syndromic intellectual disability, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked 99, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability.
BP4
Computational evidence support a benign effect (MetaRNN=0.21816692).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP9XNM_001039591.3 linkc.80C>T p.Pro27Leu missense_variant Exon 2 of 45 ENST00000378308.7 NP_001034680.2 Q93008-1Q86X58Q6P468

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP9XENST00000378308.7 linkc.80C>T p.Pro27Leu missense_variant Exon 2 of 45 5 NM_001039591.3 ENSP00000367558.2 Q93008-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.00000557
AC:
1
AN:
179403
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
65461
show subpopulations
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000125
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097465
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
1
AN XY:
362845
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.55
.;D
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
T;T
M_CAP
Pathogenic
0.41
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.0
L;L
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.20
Sift
Benign
0.073
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.0010
B;B
Vest4
0.36
MutPred
0.16
Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);
MVP
0.14
MPC
0.76
ClinPred
0.69
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.43
gMVP
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200078810; hg19: chrX-40982961; API