Variant 8-86069529-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033126.3(PSKH2):c.94G>T(p.Ala32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,608,812 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

PSKH2
NM_033126.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

PSKH2 (HGNC:18997): (protein serine kinase H2) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

PSKH2 links:

ATP6V0D2 (HGNC:18266): (ATPase H+ transporting V0 subunit d2) Predicted to enable proton transmembrane transporter activity. Predicted to be involved in vacuolar acidification and vacuolar transport. Located in apical plasma membrane. Part of vacuolar proton-transporting V-type ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ATP6V0D2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027037501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSKH2	NM_033126.3 linkuse as main transcript	c.94G>T	p.Ala32Ser	missense_variant	1/3	ENST00000276616.3	NP_149117.1
PSKH2	XM_017013929.2 linkuse as main transcript	c.380G>T	p.Arg127Leu	missense_variant	2/5		XP_016869418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PSKH2	ENST00000276616.3 linkuse as main transcript	c.94G>T	p.Ala32Ser	missense_variant	1/3	1	NM_033126.3	ENSP00000276616	P1
ATP6V0D2	ENST00000521564.1 linkuse as main transcript	c.-170+3049C>A		intron_variant		3		ENSP00000429731
PSKH2	ENST00000517981.5 linkuse as main transcript	n.168+4587G>T		intron_variant, non_coding_transcript_variant		3
PSKH2	ENST00000523010.1 linkuse as main transcript	n.228+4587G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000293

AC:

AN:

225236

Hom.:

AF XY:

0.000337

AC XY:

AN XY:

124734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.000536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000504

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000445

Gnomad OTH exome

AF:

0.000364

GnomAD4 exome

AF:

0.000376

AC:

547

AN:

1456502

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

280

AN XY:

724334

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.000578

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000560

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.000550

GnomAD4 genome

AF:

0.000355

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000448

Hom.:

Bravo

AF:

0.000431

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000622

AC:

ExAC

AF:

0.000287

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.94G>T (p.A32S) alteration is located in exon 1 (coding exon 1) of the PSKH2 gene. This alteration results from a G to T substitution at nucleotide position 94, causing the alanine (A) at amino acid position 32 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.25

DANN

Benign

0.84

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.28

M_CAP

Benign

0.0078

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

0.29

REVEL

Benign

0.012

Sift

Benign

0.45

Sift4G

Benign

0.72

Polyphen

0.050

Vest4

0.13

MVP

0.54

MPC

0.064

ClinPred

0.013

GERP RS

1.3

Varity_R

0.028

gMVP

0.13

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.

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