15-43801560-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001199885.1(HYPK):c.229G>A(p.Gly77Arg) variant causes a missense 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. 10/13 in silico tools predict 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_001199885.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.605

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]

HYPK links:

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]

SERF2 links:

SERF2-C15ORF63 (HGNC:):

SERF2-C15ORF63 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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.

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 rank	MANE	Protein	UniProt
HYPK	NM_016400.4 link	c.261G>A	p.Leu87Leu	synonymous_variant	Exon 3 of 4	ENST00000442995.4	NP_057484.4	Q9NX55-2A0A024R5Q1
HYPK	NM_001199885.1 link	c.229G>A	p.Gly77Arg	missense_variant	Exon 2 of 3		NP_001186814.1	Q9NX55
SERF2-C15ORF63	NR_037673.1 link	n.906G>A		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYPK	ENST00000442995.4 link	c.261G>A	p.Leu87Leu	synonymous_variant	Exon 3 of 4	1	NM_016400.4	ENSP00000401155.3		Q9NX55-2

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1898

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00327

AC:

821

AN:

251370

Hom.:

AF XY:

0.00238

AC XY:

324

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0457

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00123

AC:

1803

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

775

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0441

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00323

GnomAD4 genome

AF:

0.0126

AC:

1915

AN:

152294

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

912

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0437

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.0135

ESP6500AA

AF:

0.0457

AC:

201

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00390

AC:

474

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.034

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

PROVEAN

Benign

3.6

REVEL

Benign

0.076

Sift

Pathogenic

0.0

Sift4G

Benign

0.13

Vest4

0.15

MutPred

0.19

Gain of MoRF binding (P = 0.0284);

MVP

0.48

ClinPred

0.068

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over