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GeneBe

15-43800641-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016400.4(HYPK):c.19G>A(p.Val7Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

HYPK
NM_016400.4 missense

Scores

2
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.27
Variant links:
Genes affected
HYPK (HGNC:18418): (huntingtin interacting protein K) Enables protein N-terminus binding activity. Involved in negative regulation of apoptotic process and protein stabilization. Located in cytoplasm; microtubule cytoskeleton; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
SERF2 (HGNC:10757): (small EDRK-rich factor 2) Involved in protein destabilization. Predicted to be located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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;
BP4
Computational evidence support a benign effect (MetaRNN=0.2967204).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HYPKNM_016400.4 linkuse as main transcriptc.19G>A p.Val7Met missense_variant 1/4 ENST00000442995.4
SERF2-C15ORF63NR_037673.1 linkuse as main transcriptn.664G>A non_coding_transcript_exon_variant 3/6
HYPKNM_001199885.1 linkuse as main transcriptc.43G>A p.Val15Met missense_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HYPKENST00000442995.4 linkuse as main transcriptc.19G>A p.Val7Met missense_variant 1/41 NM_016400.4 P1Q9NX55-2

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000579
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:
0.0000361
AC:
9
AN:
249468
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135088
show subpopulations
Gnomad AFR exome
AF:
0.000557
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.000579
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:
0.000215
Hom.:
0
Bravo
AF:
0.000196
ESP6500AA
AF:
0.000910
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 13, 2023The c.43G>A (p.V15M) alteration is located in exon 1 (coding exon 1) of the HYPK gene. This alteration results from a G to A substitution at nucleotide position 43, causing the valine (V) at amino acid position 15 to be replaced by a methionine (M). 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
0.25
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
-0.020
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Benign
0.0086
T;T;T
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.6
L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.30
N;N;N
REVEL
Benign
0.18
Sift
Benign
0.21
T;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
0.99
D;D;.
Vest4
0.60
MVP
0.82
MPC
0.71
ClinPred
0.25
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.78

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: rs144863738; hg19: chr15-44092839; API