2-162384772-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033272.4(KCNH7):​c.2878G>C​(p.Gly960Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,862 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KCNH7
NM_033272.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08921021).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNH7NM_033272.4 linkc.2878G>C p.Gly960Arg missense_variant Exon 13 of 16 ENST00000332142.10 NP_150375.2 Q9NS40-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNH7ENST00000332142.10 linkc.2878G>C p.Gly960Arg missense_variant Exon 13 of 16 1 NM_033272.4 ENSP00000331727.5 Q9NS40-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
151816
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460862
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726746
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000132
AC:
2
AN:
151816
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74150
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2878G>C (p.G960R) alteration is located in exon 13 (coding exon 13) of the KCNH7 gene. This alteration results from a G to C substitution at nucleotide position 2878, causing the glycine (G) at amino acid position 960 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Uncertain
0.017
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
20
DANN
Benign
0.95
DEOGEN2
Benign
0.051
.;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.089
T;T
MetaSVM
Uncertain
0.00030
D
MutationAssessor
Benign
0.41
.;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.74
.;N
REVEL
Uncertain
0.36
Sift
Benign
0.48
.;T
Sift4G
Benign
0.38
T;T
Polyphen
0.0
.;B
Vest4
0.18
MutPred
0.17
.;Gain of phosphorylation at S963 (P = 0.094);
MVP
0.22
MPC
0.11
ClinPred
0.11
T
GERP RS
3.8
Varity_R
0.053
gMVP
0.19

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: rs1686525989; hg19: chr2-163241282; API