chr8-42950396-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_032410.4(HOOK3):​c.409C>G​(p.Gln137Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,607,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

HOOK3
NM_032410.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61
Variant links:
Genes affected
HOOK3 (HGNC:23576): (hook microtubule tethering protein 3) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOOK3NM_032410.4 linkc.409C>G p.Gln137Glu missense_variant Exon 6 of 22 ENST00000307602.9 NP_115786.1 Q86VS8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOOK3ENST00000307602.9 linkc.409C>G p.Gln137Glu missense_variant Exon 6 of 22 1 NM_032410.4 ENSP00000305699.3 Q86VS8
HOOK3ENST00000527306.1 linkn.595C>G non_coding_transcript_exon_variant Exon 6 of 16 1
HOOK3ENST00000533539.2 linkc.409C>G p.Gln137Glu missense_variant Exon 6 of 23 3 ENSP00000433953.2 H0YDM4

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152058
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250444
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135406
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1455082
Hom.:
0
Cov.:
27
AF XY:
0.0000180
AC XY:
13
AN XY:
724178
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:
0.0000190
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152058
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.409C>G (p.Q137E) alteration is located in exon 6 (coding exon 6) of the HOOK3 gene. This alteration results from a C to G substitution at nucleotide position 409, causing the glutamine (Q) at amino acid position 137 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.081
T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.23
Sift
Benign
0.031
D
Sift4G
Uncertain
0.054
T
Polyphen
0.95
P
Vest4
0.60
MutPred
0.72
Loss of ubiquitination at K132 (P = 0.0982);
MVP
0.44
MPC
0.56
ClinPred
0.62
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.59
gMVP
0.28

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: rs774290079; hg19: chr8-42805539; API