3-156120848-C-G

Variant names:

• chr3-156120848-C-G
• rs9812862
• NM_172160.3:c.237C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172160.3(KCNAB1):​c.237C>G​(p.Ser79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. S79S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KCNAB1 NM_172160.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 0 publications found

Genes affected

KCNAB1 (HGNC:6228): (potassium voltage-gated channel subfamily A regulatory beta subunit 1) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member includes distinct isoforms which are encoded by alternatively spliced transcript variants of this gene. Some of these isoforms are beta subunits, which form heteromultimeric complexes with alpha subunits and modulate the activity of the pore-forming alpha subunits. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14642015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172160.3. 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
	KCNAB1	NM_172160.3	MANE Select	c.237C>G	p.Ser79Arg	missense	Exon 1 of 14	NP_751892.1	Q14722-1
	KCNAB1	NM_001308217.1		c.237C>G	p.Ser79Arg	missense	Exon 1 of 13	NP_001295146.1	Q14722

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNAB1	ENST00000490337.6	TSL:1 MANE Select	c.237C>G	p.Ser79Arg	missense	Exon 1 of 14	ENSP00000419952.1	Q14722-1
	KCNAB1	ENST00000389636.9	TSL:2	c.237C>G	p.Ser79Arg	missense	Exon 1 of 13	ENSP00000374287.5	B7Z8E5
	KCNAB1	ENST00000472028.5	TSL:4	c.29+2509C>G		intron	N/A	ENSP00000420755.1	C9JBV8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.16
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.066
Sift	Benign	0.19	T
Sift4G	Benign	0.15	T
Polyphen		0.50	P
Vest4		0.18
MutPred		0.73		Gain of loop (P = 0.0312)
MVP		0.36
MPC		0.65
ClinPred		0.15	T
GERP RS		-0.11
PromoterAI		-0.018	Neutral
Varity_R		0.15
gMVP		0.51
Mutation Taster		=95/5	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9812862; hg19: chr3-155838637;