NM_019842.4:c.399-31848G>A

Variant names:

• chr6-72972060-G-A
• rs9360623
• NM_019842.4:c.399-31848G>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.399-31848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,146 control chromosomes in the GnomAD database, including 59,027 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 0.88 (59027 hom., cov: 31)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• 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

LOC105377855 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.399-31848G>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.399-31848G>A		intron_variant	Intron 1 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133522 AN: 152028 Hom.: 58994 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.878 AC: 133607 AN: 152146 Hom.: 59027 Cov.: 31 AF XY: 0.878 AC XY: 65345 AN XY: 74390

African (AFR) AF: 0.796 AC: 33021 AN: 41460

American (AMR) AF: 0.825 AC: 12617 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4142 AN: 5166

South Asian (SAS) AF: 0.886 AC: 4272 AN: 4824

European-Finnish (FIN) AF: 0.937 AC: 9937 AN: 10604

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63370 AN: 68022

Other (OTH) AF: 0.901 AC: 1900 AN: 2108

Alfa AF: 0.914 Hom.: 271703

Bravo AF: 0.865

Asia WGS AF: 0.824 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.69
PhyloP100		-0.27
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: rs9360623; hg19: chr6-73681783;