9-83796925-A-G

Position:

• chr9-83796925-A-G

Variant summary

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

The NM_025211.4(GKAP1):​c.360+2260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,058 control chromosomes in the GnomAD database, including 23,670 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 0.55 (23670 hom., cov: 32)
• Consequence: GKAP1 NM_025211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

GKAP1 (HGNC:17496): (G kinase anchoring protein 1) This gene encodes a protein that is highly similar to the mouse cGMP-dependent protein kinase anchoring protein 42kDa. The mouse protein has been found to localize with the Golgi and recruit cGMP-dependent protein kinase I alpha to the Golgi in mouse testes. It is thought to play a role in germ cell development. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GKAP1	NM_025211.4	c.360+2260T>C		intron_variant		ENST00000376371.7	NP_079487.2
GKAP1	NM_001135953.2	c.360+2260T>C		intron_variant			NP_001129425.1
GKAP1	XM_005252241.3	c.360+2260T>C		intron_variant			XP_005252298.1
GKAP1	XM_011519058.3	c.360+2260T>C		intron_variant			XP_011517360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GKAP1	ENST00000376371.7	c.360+2260T>C		intron_variant		1	NM_025211.4	ENSP00000365550.2
GKAP1	ENST00000376365.7	c.360+2260T>C		intron_variant		1		ENSP00000365544.3
GKAP1	ENST00000388782.8	n.360+2260T>C		intron_variant		2		ENSP00000373434.4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83137 AN: 151940 Hom.: 23659 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.547 AC: 83174 AN: 152058 Hom.: 23670 Cov.: 32 AF XY: 0.546 AC XY: 40602 AN XY: 74296

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.570

Alfa AF: 0.558 Hom.: 4555

Bravo AF: 0.552

Asia WGS AF: 0.588 AC: 2045 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	0.45
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: rs918223; hg19: chr9-86411840;