16-67909485-C-G

Position:

• chr16-67909485-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006742.3(PSKH1):​c.736C>G​(p.Arg246Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PSKH1 NM_006742.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

Genes affected

PSKH1 (HGNC:9529): (protein serine kinase H1) Predicted to enable protein kinase activity. Predicted to act upstream of or within determination of left/right symmetry; heart development; and protein phosphorylation. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34585893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSKH1	NM_006742.3	c.736C>G	p.Arg246Gly	missense_variant	2/3	ENST00000291041.6	NP_006733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSKH1	ENST00000291041.6	c.736C>G	p.Arg246Gly	missense_variant	2/3	1	NM_006742.3	ENSP00000291041.4
PSKH1	ENST00000570631.5	c.736C>G	p.Arg246Gly	missense_variant	2/2	1		ENSP00000482880.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461448 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726998

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

The c.736C>G (p.R246G) alteration is located in exon 2 (coding exon 1) of the PSKH1 gene. This alteration results from a C to G substitution at nucleotide position 736, causing the arginine (R) at amino acid position 246 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	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.065	.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.065	.;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.28
Sift	Benign	0.49	.;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0010	.;B
Vest4		0.58
MutPred		0.57		Loss of stability (P = 0.0025);Loss of stability (P = 0.0025);
MVP		0.77
MPC		1.5
ClinPred		0.69	D
GERP RS		4.5
Varity_R		0.26
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67943388;