rs2759387

Variant names:

• chr6-163418636-T-C
• rs2759387
• NM_006775.3:c.142+3301T>C

Variant summary

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

The NM_006775.3(QKI):​c.142+3301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,092 control chromosomes in the GnomAD database, including 3,115 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 0.19 (3115 hom., cov: 32)
• Consequence: QKI NM_006775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QKI	NM_006775.3	c.142+3301T>C		intron_variant	Intron 1 of 7	ENST00000361752.8	NP_006766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QKI	ENST00000361752.8	c.142+3301T>C		intron_variant	Intron 1 of 7	1	NM_006775.3	ENSP00000355094.3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28453 AN: 151974 Hom.: 3116 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.187 AC: 28459 AN: 152092 Hom.: 3115 Cov.: 32 AF XY: 0.184 AC XY: 13666 AN XY: 74376

African (AFR) AF: 0.0925 AC: 3840 AN: 41510

American (AMR) AF: 0.182 AC: 2786 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3466

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5190

South Asian (SAS) AF: 0.164 AC: 790 AN: 4824

European-Finnish (FIN) AF: 0.228 AC: 2408 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17027 AN: 67912

Other (OTH) AF: 0.211 AC: 446 AN: 2114

Alfa AF: 0.209 Hom.: 426

Bravo AF: 0.183

Asia WGS AF: 0.0730 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.48
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: rs2759387; hg19: chr6-163839668; COSMIC: COSV51691146; COSMIC: COSV51691146;