Variant chr8-86064465-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033126.3(PSKH2):c.352C>G(p.Arg118Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000015 ( 0 hom. )

Consequence

PSKH2
NM_033126.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0810

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:

PSKH2 (HGNC:):

PSKH2 links:

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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=0.093687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSKH2	NM_033126.3 linkuse as main transcript	c.352C>G	p.Arg118Gly	missense_variant	2/3	ENST00000276616.3	NP_149117.1	Q96QS6
PSKH2	XM_017013929.2 linkuse as main transcript	c.709C>G	p.Arg237Gly	missense_variant	4/5		XP_016869418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSKH2	ENST00000276616.3 linkuse as main transcript	c.352C>G	p.Arg118Gly	missense_variant	2/3	1	NM_033126.3	ENSP00000276616.2	Q96QS6
ATP6V0D2	ENST00000521564.1 linkuse as main transcript	c.-262-1923G>C		intron_variant		3		ENSP00000429731.1	E5RHJ7
PSKH2	ENST00000517981.5 linkuse as main transcript	n.335C>G		non_coding_transcript_exon_variant	3/3	3
PSKH2	ENST00000523010.1 linkuse as main transcript	n.395C>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251362

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727234

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:

0.0000198

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

May 13, 2022

The c.352C>G (p.R118G) alteration is located in exon 2 (coding exon 2) of the PSKH2 gene. This alteration results from a C to G substitution at nucleotide position 352, causing the arginine (R) at amino acid position 118 to be replaced by a glycine (G). 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

0.085

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.0

DANN

Benign

0.85

DEOGEN2

Benign

0.016

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.77

M_CAP

Benign

0.0094

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.3

REVEL

Benign

0.042

Sift

Benign

0.16

Sift4G

Benign

0.16

Polyphen

0.021

Vest4

0.25

MutPred

0.51

Loss of MoRF binding (P = 0.0068);

MVP

0.42

MPC

0.11

ClinPred

0.042

GERP RS

-3.4

Varity_R

0.067

gMVP

0.057

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