rs6592284

chr11-86344859-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000533986.5(HIKESHI):c.*92T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 613,048 control chromosomes in the GnomAD database, including 13,883 homozygotes. 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: 𝑓 0.23 (4864 hom., cov: 32)
  • Exomes 𝑓: 0.19 (9019 hom.)
• Consequence: HIKESHI ENST00000533986.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976

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]

LOC105369421 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIKESHI	NM_016401.4	c.539+138T>C		intron_variant		ENST00000278483.8
LOC105369421	XR_007062826.1	n.354-7926A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIKESHI	ENST00000278483.8	c.539+138T>C		intron_variant		1	NM_016401.4	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34455 AN: 152076 Hom.: 4866 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.186 AC: 85921 AN: 460854 Hom.: 9019 Cov.: 6 AF XY: 0.188 AC XY: 45400 AN XY: 241548

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.0825

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.226 AC: 34470 AN: 152194 Hom.: 4864 Cov.: 32 AF XY: 0.225 AC XY: 16738 AN XY: 74418

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.203

Alfa AF: 0.170 Hom.: 5891

Bravo AF: 0.247

Asia WGS AF: 0.292 AC: 1015 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.6
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6592284; hg19: chr11-86055901; COSMIC: COSV53575132;