NM_001161352.2:c.3318C>G

Variant names:

• chr10-76891549-G-C
• rs779632278
• NM_001161352.2:c.3318C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001161352.2(KCNMA1):​c.3318C>G​(p.Leu1106Leu) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. L1106L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNMA1 NM_001161352.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• Publications: 2 publications found

Genes affected

KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

KCNMA1-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.042).
• BP7: Synonymous conserved (PhyloP=0.497 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161352.2. 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
	KCNMA1	NM_001161352.2	MANE Select	c.3318C>G	p.Leu1106Leu	synonymous	Exon 26 of 28	NP_001154824.1
	KCNMA1	NM_001437422.1		c.3276C>G	p.Leu1092Leu	synonymous	Exon 26 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.3267C>G	p.Leu1089Leu	synonymous	Exon 26 of 28	NP_001154825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.3318C>G	p.Leu1106Leu	synonymous	Exon 26 of 28	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.3267C>G	p.Leu1089Leu	synonymous	Exon 26 of 28	ENSP00000485867.1
	KCNMA1	ENST00000639406.1	TSL:1	c.3234C>G	p.Leu1078Leu	synonymous	Exon 27 of 29	ENSP00000491732.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250000 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		0.50

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: rs779632278; hg19: chr10-78651307;