GeneBe

rs140959967

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_031407.7(HUWE1):​c.3966G>C​(p.Leu1322Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000919 in 1,088,259 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. Synonymous variant affecting the same amino acid position (i.e. L1322L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

HUWE1
NM_031407.7 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.508

Publications

0 publications found
Variant links:
Genes affected
HUWE1 (HGNC:30892): (HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1) This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]
HUWE1 Gene-Disease associations (from GenCC):
  • intellectual disability, X-linked syndromic, Turner type
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, G2P
  • non-syndromic X-linked intellectual disability
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
  • syndromic intellectual disability
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (REVEL=0.035).
BP7
Synonymous conserved (PhyloP=-0.508 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HUWE1NM_031407.7 linkc.3966G>C p.Leu1322Leu synonymous_variant Exon 33 of 84 ENST00000262854.11 NP_113584.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HUWE1ENST00000262854.11 linkc.3966G>C p.Leu1322Leu synonymous_variant Exon 33 of 84 1 NM_031407.7 ENSP00000262854.6

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.19e-7
AC:
1
AN:
1088259
Hom.:
0
Cov.:
29
AF XY:
0.00000282
AC XY:
1
AN XY:
354617
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26240
American (AMR)
AF:
0.00
AC:
0
AN:
35203
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19329
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
53929
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
39725
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4116
European-Non Finnish (NFE)
AF:
0.00000120
AC:
1
AN:
833713
Other (OTH)
AF:
0.00
AC:
0
AN:
45826
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
1.5
DANN
Benign
0.66
PhyloP100
-0.51
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Other links and lift over

dbSNP: rs140959967; hg19: chrX-53619364; API