NM_019842.4:c.399-70342C>A

Variant names:

• chr6-72933566-C-A
• rs7744813
• NM_019842.4:c.399-70342C>A

Variant summary

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

The NM_019842.4(KCNQ5):​c.399-70342C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,964 control chromosomes in the GnomAD database, including 33,321 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 0.66 (33321 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 38 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019842.4. 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
	KCNQ5	NM_019842.4	MANE Select	c.399-70342C>A		intron	N/A	NP_062816.2
	KCNQ5	NM_001160133.2		c.399-70342C>A		intron	N/A	NP_001153605.1	Q9NR82-6
	KCNQ5	NM_001160132.2		c.399-70342C>A		intron	N/A	NP_001153604.1	Q9NR82-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ5	ENST00000370398.6	TSL:1 MANE Select	c.399-70342C>A		intron	N/A	ENSP00000359425.1	Q9NR82-1
	KCNQ5	ENST00000629977.2	TSL:1	c.399-70342C>A		intron	N/A	ENSP00000485743.1	Q9NR82-2
	KCNQ5	ENST00000370392.5	TSL:1	c.399-70342C>A		intron	N/A	ENSP00000359419.1	Q9NR82-4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99619 AN: 151846 Hom.: 33270 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.656 AC: 99726 AN: 151964 Hom.: 33321 Cov.: 32 AF XY: 0.655 AC XY: 48631 AN XY: 74250

African (AFR) AF: 0.764 AC: 31689 AN: 41454

American (AMR) AF: 0.677 AC: 10333 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3470

East Asian (EAS) AF: 0.790 AC: 4088 AN: 5174

South Asian (SAS) AF: 0.525 AC: 2526 AN: 4816

European-Finnish (FIN) AF: 0.640 AC: 6748 AN: 10540

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40234 AN: 67938

Other (OTH) AF: 0.631 AC: 1331 AN: 2110

Alfa AF: 0.627 Hom.: 63679

Bravo AF: 0.673

Asia WGS AF: 0.623 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		0.12
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: rs7744813; hg19: chr6-73643289;