NM_019842.4:c.398+82419G>A

Variant names:

• chr6-72705006-G-A
• rs16882712
• NM_019842.4:c.398+82419G>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.398+82419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,062 control chromosomes in the GnomAD database, including 1,488 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 0.10 (1488 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.398+82419G>A		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+82419G>A		intron_variant	Intron 1 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15889 AN: 151944 Hom.: 1483 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0612

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.105 AC: 15926 AN: 152062 Hom.: 1488 Cov.: 32 AF XY: 0.101 AC XY: 7486 AN XY: 74326

African (AFR) AF: 0.249 AC: 10331 AN: 41440

American (AMR) AF: 0.0691 AC: 1056 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0612 AC: 212 AN: 3462

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0150 AC: 72 AN: 4808

European-Finnish (FIN) AF: 0.0440 AC: 466 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3513 AN: 67970

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.0856 Hom.: 180

Bravo AF: 0.115

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		0.97
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: rs16882712; hg19: chr6-73414730;