6-163453315-T-C

Variant names:

• chr6-163453315-T-C
• rs7758706
• NM_006775.3:c.143-1964T>C

Variant summary

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

The NM_006775.3(QKI):​c.143-1964T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 152,144 control chromosomes in the GnomAD database, including 836 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 0.097 (836 hom., cov: 32)
• Consequence: QKI NM_006775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QKI	NM_006775.3	c.143-1964T>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.143-1964T>C		intron_variant	Intron 1 of 7	1	NM_006775.3	ENSP00000355094.3

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14694 AN: 152026 Hom.: 833 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0966 AC: 14695 AN: 152144 Hom.: 836 Cov.: 32 AF XY: 0.0988 AC XY: 7352 AN XY: 74410

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0476

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0862 Hom.: 561

Bravo AF: 0.103

Asia WGS AF: 0.178 AC: 611 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7758706; hg19: chr6-163874347;