Variant 8-86064447-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033126.3(PSKH2):c.370A>C(p.Met124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.00049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSKH2
NM_033126.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.235

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02969116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSKH2	NM_033126.3 link	c.370A>C	p.Met124Leu	missense_variant	2/3	ENST00000276616.3	NP_149117.1	Q96QS6
PSKH2	XM_017013929.2 link	c.727A>C	p.Met243Leu	missense_variant	4/5		XP_016869418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSKH2	ENST00000276616.3 link	c.370A>C	p.Met124Leu	missense_variant	2/3	1	NM_033126.3	ENSP00000276616.2	Q96QS6
ATP6V0D2	ENST00000521564.1 link	c.-262-1941T>G		intron_variant		3		ENSP00000429731.1	E5RHJ7
PSKH2	ENST00000517981.5 link	n.353A>C		non_coding_transcript_exon_variant	3/3	3
PSKH2	ENST00000523010.1 link	n.413A>C		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000486

AC:

706

AN:

1453998

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

307

AN XY:

723614

show subpopulations

Gnomad4 AFR exome

AF:

0.000390

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000586

Gnomad4 OTH exome

AF:

0.000433

GnomAD4 genome

Cov.:

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

Aug 26, 2024

The c.370A>C (p.M124L) alteration is located in exon 2 (coding exon 2) of the PSKH2 gene. This alteration results from a A to C substitution at nucleotide position 370, causing the methionine (M) at amino acid position 124 to be replaced by a leucine (L). 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

0.095

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.043

DANN

Benign

0.54

DEOGEN2

Benign

0.00073

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.19

M_CAP

Benign

0.0049

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

PrimateAI

Benign

0.29

PROVEAN

Benign

0.25

REVEL

Benign

0.062

Sift

Benign

0.65

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.17

MutPred

0.47

Loss of MoRF binding (P = 0.0832);

MVP

0.10

MPC

0.064

ClinPred

0.052

GERP RS

-8.9

Varity_R

0.053

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over