15-43800634-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016400.4(HYPK):​c.12G>C​(p.Glu4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

HYPK
NM_016400.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.260
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1116887).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HYPKNM_016400.4 linkc.12G>C p.Glu4Asp missense_variant Exon 1 of 4 ENST00000442995.4 NP_057484.4 Q9NX55-2A0A024R5Q1
HYPKNM_001199885.1 linkc.36G>C p.Glu12Asp missense_variant Exon 1 of 3 NP_001186814.1 Q9NX55
SERF2-C15ORF63NR_037673.1 linkn.657G>C non_coding_transcript_exon_variant Exon 3 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HYPKENST00000442995.4 linkc.12G>C p.Glu4Asp missense_variant Exon 1 of 4 1 NM_016400.4 ENSP00000401155.3 Q9NX55-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249632
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135176
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:
0.00000891
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461844
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727224
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:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.36G>C (p.E12D) alteration is located in exon 1 (coding exon 1) of the HYPK gene. This alteration results from a G to C substitution at nucleotide position 36, causing the glutamic acid (E) at amino acid position 12 to be replaced by an aspartic acid (D). 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
0.13
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.011
T;T;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.58
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.83
.;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;L;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.69
N;N;N
REVEL
Benign
0.064
Sift
Benign
0.11
T;T;D
Sift4G
Benign
0.20
T;T;T
Polyphen
0.0020
B;B;.
Vest4
0.47
MutPred
0.19
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.31
MPC
0.63
ClinPred
0.11
T
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs375981580; hg19: chr15-44092832; API