11-86306313-C-G

Variant summary

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

The NM_001322407.2(HIKESHI):​c.-19C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,282 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

HIKESHI
NM_001322407.2 5_prime_UTR_premature_start_codon_gain

Scores

11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29
Variant links:
Genes affected
HIKESHI (HGNC:26938): (heat shock protein nuclear import factor hikeshi) This gene encodes an evolutionarily conserved nuclear transport receptor that mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins. The protein mediates transport of the ATP form but not the ADP form of Hsp70 proteins under conditions of heat shock stress. Structural analyses demonstrate that the protein forms an asymmetric homodimer and that the N-terminal domain consists of a jelly-roll/beta-sandwich fold structure that contains hydrophobic pockets involved in FG-nucleoporin recognition. Reduction of RNA expression levels in HeLa cells using small interfering RNAs results in inhibition of heat shock-induced nuclear accumulation of Hsp70s, indicating a role for this gene in regulation of Hsp70 nuclear import during heat shock stress. [provided by RefSeq, Apr 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HIKESHINM_016401.4 linkc.99C>G p.Ile33Met missense_variant Exon 2 of 5 ENST00000278483.8 NP_057485.2 Q53FT3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HIKESHIENST00000278483.8 linkc.99C>G p.Ile33Met missense_variant Exon 2 of 5 1 NM_016401.4 ENSP00000278483.3 Q53FT3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152282
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.043
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
.;T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.5
.;M
PROVEAN
Benign
-2.4
N;N
REVEL
Benign
0.20
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.98
D;D
Vest4
0.52
MutPred
0.68
Loss of catalytic residue at I33 (P = 0.0049);Loss of catalytic residue at I33 (P = 0.0049);
MVP
0.32
MPC
0.88
ClinPred
0.95
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr11-86017355; API