2-162373516-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_033272.4(KCNH7):c.3278C>T(p.Pro1093Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,575,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
KCNH7
NM_033272.4 missense
NM_033272.4 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 3.02
Publications
1 publications found
Genes affected
KCNH7 (HGNC:18863): (potassium voltage-gated channel subfamily H member 7) Voltage-gated potassium (Kv) 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. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms. [provided by RefSeq, Jul 2008]
GCA (HGNC:15990): (grancalcin) This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.233598).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000329 AC: 5AN: 152086Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
5
AN:
152086
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000180 AC: 4AN: 222598 AF XY: 0.0000248 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
222598
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000105 AC: 15AN: 1423708Hom.: 0 Cov.: 31 AF XY: 0.00000565 AC XY: 4AN XY: 707608 show subpopulations
GnomAD4 exome
AF:
AC:
15
AN:
1423708
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
707608
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31444
American (AMR)
AF:
AC:
0
AN:
39364
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25156
East Asian (EAS)
AF:
AC:
1
AN:
36916
South Asian (SAS)
AF:
AC:
2
AN:
80742
European-Finnish (FIN)
AF:
AC:
0
AN:
52780
Middle Eastern (MID)
AF:
AC:
0
AN:
5666
European-Non Finnish (NFE)
AF:
AC:
11
AN:
1092800
Other (OTH)
AF:
AC:
1
AN:
58840
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000329 AC: 5AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74272 show subpopulations
GnomAD4 genome
AF:
AC:
5
AN:
152086
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74272
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41418
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5170
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
4
AN:
68014
Other (OTH)
AF:
AC:
0
AN:
2082
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
3
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Nov 17, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.3278C>T (p.P1093L) alteration is located in exon 15 (coding exon 15) of the KCNH7 gene. This alteration results from a C to T substitution at nucleotide position 3278, causing the proline (P) at amino acid position 1093 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
.;D
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Uncertain
D;D
Polyphen
0.52
.;P
Vest4
0.22
MutPred
0.37
.;Loss of disorder (P = 0.0612);
MVP
MPC
0.095
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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