15-43801560-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_016400.4(HYPK):c.261G>A(p.Leu87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,908 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 33 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 53 hom. )
Consequence
HYPK
NM_016400.4 synonymous
NM_016400.4 synonymous
Scores
1
2
12
Clinical Significance
Conservation
PhyloP100: 0.605
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0017516911).
BP6
Variant 15-43801560-G-A is Benign according to our data. Variant chr15-43801560-G-A is described in ClinVar as [Benign]. Clinvar id is 714534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.605 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1915/152294) while in subpopulation AFR AF= 0.0437 (1818/41564). AF 95% confidence interval is 0.0421. There are 33 homozygotes in gnomad4. There are 912 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HYPK | NM_016400.4 | c.261G>A | p.Leu87= | synonymous_variant | 3/4 | ENST00000442995.4 | |
SERF2-C15ORF63 | NR_037673.1 | n.906G>A | non_coding_transcript_exon_variant | 5/6 | |||
HYPK | NM_001199885.1 | c.229G>A | p.Gly77Arg | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HYPK | ENST00000442995.4 | c.261G>A | p.Leu87= | synonymous_variant | 3/4 | 1 | NM_016400.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0125 AC: 1898AN: 152176Hom.: 32 Cov.: 32
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GnomAD3 exomes AF: 0.00327 AC: 821AN: 251370Hom.: 18 AF XY: 0.00238 AC XY: 324AN XY: 135898
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GnomAD4 exome AF: 0.00123 AC: 1803AN: 1461614Hom.: 53 Cov.: 31 AF XY: 0.00107 AC XY: 775AN XY: 727132
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GnomAD4 genome AF: 0.0126 AC: 1915AN: 152294Hom.: 33 Cov.: 32 AF XY: 0.0122 AC XY: 912AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Benign
T
Vest4
MutPred
Gain of MoRF binding (P = 0.0284);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at