rs2136648

Positions:

• chr16-67912234-T-A
• chr16-67912234-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006742.3(PSKH1):​c.957+2528T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,230 control chromosomes in the GnomAD database, including 1,914 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.092 (1914 hom., cov: 32)
• Consequence: PSKH1 NM_006742.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSKH1	NM_006742.3	c.957+2528T>A		intron_variant		ENST00000291041.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSKH1	ENST00000291041.6	c.957+2528T>A		intron_variant		1	NM_006742.3	P1

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13934 AN: 152112 Hom.: 1899 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.0669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0918 AC: 13981 AN: 152230 Hom.: 1914 Cov.: 32 AF XY: 0.0892 AC XY: 6639 AN XY: 74428

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00554

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0126 Hom.: 22

Bravo AF: 0.103

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs2136648; hg19: chr16-67946137;