rs34970857

Variant names:

• chr1-110518130-C-T
• rs34970857
• NM_005549.2:c.658G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-110518130-C-T
• chr1-110518130-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005549.2(KCNA10):​c.658G>A​(p.Val220Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,613,666 control chromosomes in the GnomAD database, including 4,459 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (320 hom., cov: 30)
  • Exomes 𝑓: 0.073 (4139 hom.)
• Consequence: KCNA10 NM_005549.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.800
• Publications: 21 publications found

Genes affected

KCNA10 (HGNC:6219): (potassium voltage-gated channel subfamily A member 10) 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 contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It is specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. This gene is intronless, and the gene is clustered with genes KCNA2 and KCNA3 on chromosome 1. [provided by RefSeq, Jul 2008]

ENSG00000301555 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024356544).
• BP6: Variant 1-110518130-C-T is Benign according to our data. Variant chr1-110518130-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005549.2. 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
	KCNA10	NM_005549.2	MANE Select	c.658G>A	p.Val220Met	missense	Exon 1 of 1	NP_005540.1	Q16322

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNA10	ENST00000369771.4	TSL:6 MANE Select	c.658G>A	p.Val220Met	missense	Exon 1 of 1	ENSP00000358786.2	Q16322
	ENSG00000301555	ENST00000779684.1		n.87-8337C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9064 AN: 151668 Hom.: 319 Cov.: 30

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0709

GnomAD2 exomes AF: 0.0684 AC: 17179 AN: 251332 AF XY: 0.0716

Gnomad AFR exome AF: 0.0286

Gnomad AMR exome AF: 0.0352

Gnomad ASJ exome AF: 0.0482

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.0520

Gnomad NFE exome AF: 0.0739

Gnomad OTH exome AF: 0.0706

GnomAD4 exome AF: 0.0725 AC: 106022 AN: 1461878 Hom.: 4139 Cov.: 73 AF XY: 0.0736 AC XY: 53497 AN XY: 727238

African (AFR) AF: 0.0276 AC: 923 AN: 33480

American (AMR) AF: 0.0362 AC: 1621 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 1245 AN: 26136

East Asian (EAS) AF: 0.0956 AC: 3795 AN: 39700

South Asian (SAS) AF: 0.101 AC: 8752 AN: 86258

European-Finnish (FIN) AF: 0.0547 AC: 2920 AN: 53420

Middle Eastern (MID) AF: 0.107 AC: 619 AN: 5768

European-Non Finnish (NFE) AF: 0.0737 AC: 81918 AN: 1111998

Other (OTH) AF: 0.0700 AC: 4229 AN: 60394

GnomAD4 genome AF: 0.0597 AC: 9058 AN: 151788 Hom.: 320 Cov.: 30 AF XY: 0.0606 AC XY: 4494 AN XY: 74118

African (AFR) AF: 0.0289 AC: 1197 AN: 41404

American (AMR) AF: 0.0508 AC: 775 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.109 AC: 557 AN: 5088

South Asian (SAS) AF: 0.106 AC: 505 AN: 4756

European-Finnish (FIN) AF: 0.0502 AC: 530 AN: 10566

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5084 AN: 67926

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0708 Hom.: 833

Bravo AF: 0.0574

TwinsUK AF: 0.0766 AC: 284

ALSPAC AF: 0.0778 AC: 300

ESP6500AA AF: 0.0311 AC: 137

ESP6500EA AF: 0.0749 AC: 644

ExAC AF: 0.0699 AC: 8485

Asia WGS AF: 0.0870 AC: 301 AN: 3478

EpiCase AF: 0.0780

EpiControl AF: 0.0751

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.80
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.83	P
Vest4		0.030
MPC		0.036
ClinPred		0.012	T
GERP RS		4.1
Varity_R		0.099
gMVP		0.55
Mutation Taster		=98/2	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: rs34970857; hg19: chr1-111060752; COSMIC: COSV63904576; COSMIC: COSV63904576;