1-110518130-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.060 ( 320 hom., cov: 30)
Exomes 𝑓: 0.073 ( 4139 hom. )

Consequence

KCNA10
NM_005549.2 missense

Scores

4
14

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.800
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNA10NM_005549.2 linkc.658G>A p.Val220Met missense_variant Exon 1 of 1 ENST00000369771.4 NP_005540.1 Q16322

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNA10ENST00000369771.4 linkc.658G>A p.Val220Met missense_variant Exon 1 of 1 6 NM_005549.2 ENSP00000358786.2 Q16322

Frequencies

GnomAD3 genomes
AF:
0.0598
AC:
9064
AN:
151668
Hom.:
319
Cov.:
30
show subpopulations
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
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0276
AC:
923
AN:
33480
Gnomad4 AMR exome
AF:
0.0362
AC:
1621
AN:
44724
Gnomad4 ASJ exome
AF:
0.0476
AC:
1245
AN:
26136
Gnomad4 EAS exome
AF:
0.0956
AC:
3795
AN:
39700
Gnomad4 SAS exome
AF:
0.101
AC:
8752
AN:
86258
Gnomad4 FIN exome
AF:
0.0547
AC:
2920
AN:
53420
Gnomad4 NFE exome
AF:
0.0737
AC:
81918
AN:
1111998
Gnomad4 Remaining exome
AF:
0.0700
AC:
4229
AN:
60394
Heterozygous variant carriers
0
6335
12670
19004
25339
31674
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
2996
5992
8988
11984
14980
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0597
AC:
9058
AN:
151788
Hom.:
320
Cov.:
30
AF XY:
0.0606
AC XY:
4494
AN XY:
74118
show subpopulations
Gnomad4 AFR
AF:
0.0289
AC:
0.0289103
AN:
0.0289103
Gnomad4 AMR
AF:
0.0508
AC:
0.0507797
AN:
0.0507797
Gnomad4 ASJ
AF:
0.0452
AC:
0.045245
AN:
0.045245
Gnomad4 EAS
AF:
0.109
AC:
0.109473
AN:
0.109473
Gnomad4 SAS
AF:
0.106
AC:
0.106182
AN:
0.106182
Gnomad4 FIN
AF:
0.0502
AC:
0.0501609
AN:
0.0501609
Gnomad4 NFE
AF:
0.0748
AC:
0.0748462
AN:
0.0748462
Gnomad4 OTH
AF:
0.0711
AC:
0.07109
AN:
0.07109
Heterozygous variant carriers
0
413
826
1238
1651
2064
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
112
224
336
448
560
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Oct 29, 2020
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26108971) -

Computational scores

Source: dbNSFP v4.3

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
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34970857; hg19: chr1-111060752; COSMIC: COSV63904576; COSMIC: COSV63904576; API