rs9458849

Variant names:

• chr6-163522193-A-G
• rs9458849
• NM_006775.3:c.403-12789A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006775.3(QKI):​c.403-12789A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,238 control chromosomes in the GnomAD database, including 555 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 0.080 (555 hom., cov: 32)
• Consequence: QKI NM_006775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 4 publications found

Genes affected

QKI (HGNC:21100): (QKI, KH domain containing RNA binding) The protein encoded by this gene is an RNA-binding protein that regulates pre-mRNA splicing, export of mRNAs from the nucleus, protein translation, and mRNA stability. The encoded protein is involved in myelinization and oligodendrocyte differentiation and may play a role in schizophrenia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006775.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QKI	NM_006775.3	MANE Select	c.403-12789A>G		intron	N/A	NP_006766.1
	QKI	NM_001301085.2		c.403-12789A>G		intron	N/A	NP_001288014.1
	QKI	NM_206854.3		c.403-12789A>G		intron	N/A	NP_996736.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QKI	ENST00000361752.8	TSL:1 MANE Select	c.403-12789A>G		intron	N/A	ENSP00000355094.3
	QKI	ENST00000361195.6	TSL:1	c.403-12789A>G		intron	N/A	ENSP00000354867.2
	QKI	ENST00000275262.11	TSL:1	c.403-12789A>G		intron	N/A	ENSP00000275262.7

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12132 AN: 152120 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0797 AC: 12133 AN: 152238 Hom.: 555 Cov.: 32 AF XY: 0.0776 AC XY: 5781 AN XY: 74452

African (AFR) AF: 0.0990 AC: 4112 AN: 41520

American (AMR) AF: 0.0688 AC: 1052 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0614 AC: 296 AN: 4824

European-Finnish (FIN) AF: 0.0444 AC: 471 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0818 AC: 5561 AN: 68010

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0239 Hom.: 12

Bravo AF: 0.0820

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.57
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9458849; hg19: chr6-163943225;