rs748048916

Variant names:

• chr8-86048737-C-A
• NM_033126.3:c.883G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-86048737-C-A
• chr8-86048737-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033126.3(PSKH2):​c.883G>T​(p.Asp295Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D295N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PSKH2 NM_033126.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSKH2	NM_033126.3	c.883G>T	p.Asp295Tyr	missense_variant	Exon 3 of 3	ENST00000276616.3	NP_149117.1
PSKH2	XM_017013929.2	c.1240G>T	p.Asp414Tyr	missense_variant	Exon 5 of 5		XP_016869418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSKH2	ENST00000276616.3	c.883G>T	p.Asp295Tyr	missense_variant	Exon 3 of 3	1	NM_033126.3	ENSP00000276616.2
ATP6V0D2	ENST00000521564.1	c.-262-17651C>A		intron_variant	Intron 1 of 3	3		ENSP00000429731.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458352 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724978

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.5	M
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.74		Gain of ubiquitination at K299 (P = 0.1191);
MVP		0.75
MPC		0.45
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.68
gMVP		0.71

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.

Other links and lift over

hg19: chr8-87060966;