rs993314

Variant names:

• chr6-72728849-T-C
• rs993314
• NM_019842.4:c.398+106262T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

KCNQ5 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 46

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.398+106262T>C		intron_variant	Intron 1 of 13	ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.398+106262T>C		intron_variant	Intron 1 of 13	1	NM_019842.4	ENSP00000359425.1

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

African (AFR) AF: 0.673 AC: 27903 AN: 41436

American (AMR) AF: 0.457 AC: 6980 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2785 AN: 5172

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4816

European-Finnish (FIN) AF: 0.168 AC: 1780 AN: 10594

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12680 AN: 67994

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.246 Hom.: 3016

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
PhyloP100		1.4
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: rs993314; hg19: chr6-73438572;