rs993314

Positions:

• chr6-72728849-T-C

Variant summary

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

The NM_019842.4(KCNQ5):​c.398+106262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,078 control chromosomes in the GnomAD database, including 13,799 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 0.37 (13799 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

KCNQ5 (HGNC:6299): (potassium voltage-gated channel subfamily Q member 5) This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.398+106262T>C		intron_variant		ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.398+106262T>C		intron_variant		1	NM_019842.4	ENSP00000359425	P4

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55510 AN: 151960 Hom.: 13744 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.366 AC: 55629 AN: 152078 Hom.: 13799 Cov.: 32 AF XY: 0.369 AC XY: 27445 AN XY: 74358

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.341

Alfa AF: 0.244 Hom.: 2629

Bravo AF: 0.403

Asia WGS AF: 0.484 AC: 1680 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.85

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: rs993314; hg19: chr6-73438572;