2-162371906-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_033272.4(KCNH7):​c.3514C>A​(p.Pro1172Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,506 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KCNH7
NM_033272.4 missense

Scores

5
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.53

Publications

0 publications found
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]
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21060982).
BP6
Variant 2-162371906-G-T is Benign according to our data. Variant chr2-162371906-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 4041607.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNH7NM_033272.4 linkc.3514C>A p.Pro1172Thr missense_variant Exon 16 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.3514C>A p.Pro1172Thr missense_variant Exon 16 of 16 1 NM_033272.4 ENSP00000331727.5 Q9NS40-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250936
AF XY:
0.00000737
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461506
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727066
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33466
American (AMR)
AF:
0.00
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39668
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53392
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111762
Other (OTH)
AF:
0.00
AC:
0
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 10, 2025
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.047
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
19
DANN
Benign
0.93
DEOGEN2
Benign
0.37
.;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.067
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Uncertain
0.79
D
MutationAssessor
Uncertain
2.3
.;M
PhyloP100
4.5
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-2.8
.;D
REVEL
Uncertain
0.43
Sift
Benign
0.092
.;T
Sift4G
Benign
0.15
T;T
Polyphen
0.010
.;B
Vest4
0.090
MutPred
0.33
.;Loss of glycosylation at P1172 (P = 0.0658);
MVP
0.72
MPC
0.11
ClinPred
0.24
T
GERP RS
4.5
Varity_R
0.19
gMVP
0.55
Mutation Taster
=82/18
polymorphism

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

Other links and lift over

dbSNP: rs750033552; hg19: chr2-163228416; API