NM_019842.4:c.1577+3661G>T

Variant names:

• chr6-73173515-G-T
• rs3823118
• NM_019842.4:c.1577+3661G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019842.4(KCNQ5):​c.1577+3661G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ5	NM_019842.4	MANE Select	c.1577+3661G>T		intron	N/A	NP_062816.2
	KCNQ5	NM_001160133.2		c.1634+3661G>T		intron	N/A	NP_001153605.1
	KCNQ5	NM_001160132.2		c.1607+3661G>T		intron	N/A	NP_001153604.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ5	ENST00000370398.6	TSL:1 MANE Select	c.1577+3661G>T		intron	N/A	ENSP00000359425.1
	KCNQ5	ENST00000629977.2	TSL:1	c.1550+3661G>T		intron	N/A	ENSP00000485743.1
	KCNQ5	ENST00000342056.6	TSL:5	c.1634+3661G>T		intron	N/A	ENSP00000345055.2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		0.35

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: rs3823118; hg19: chr6-73883238;