NM_153033.5:c.-181T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153033.5(KCTD7):​c.-181T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 488,210 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: 29)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

KCTD7
NM_153033.5 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

Publications

1 publications found
Variant links:
Genes affected
KCTD7 (HGNC:21957): (potassium channel tetramerization domain containing 7) This gene encodes a member of the potassium channel tetramerization domain-containing protein family. Family members are identified on a structural basis and contain an amino-terminal domain similar to the T1 domain present in the voltage-gated potassium channel. Mutations in this gene have been associated with progressive myoclonic epilepsy-3. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]
KCTD7 Gene-Disease associations (from GenCC):
  • progressive myoclonic epilepsy type 3
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • progressive myoclonus epilepsy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

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 (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCTD7NM_153033.5 linkc.-181T>G 5_prime_UTR_variant Exon 1 of 4 ENST00000639828.2 NP_694578.1 Q96MP8-1A0A024RDN7
KCTD7NM_001167961.2 linkc.-181T>G 5_prime_UTR_variant Exon 1 of 5 NP_001161433.1 Q96MP8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCTD7ENST00000639828.2 linkc.-181T>G 5_prime_UTR_variant Exon 1 of 4 2 NM_153033.5 ENSP00000492240.1 Q96MP8-1
ENSG00000284461ENST00000503687.2 linkn.-181T>G upstream_gene_variant 2 ENSP00000421074.1 E9PHB8

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151896
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000208
AC:
7
AN:
336314
Hom.:
0
Cov.:
5
AF XY:
0.0000230
AC XY:
4
AN XY:
174286
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
7306
American (AMR)
AF:
0.00
AC:
0
AN:
6266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
8632
East Asian (EAS)
AF:
0.00
AC:
0
AN:
19302
South Asian (SAS)
AF:
0.00
AC:
0
AN:
16842
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
22830
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1352
European-Non Finnish (NFE)
AF:
0.0000298
AC:
7
AN:
235266
Other (OTH)
AF:
0.00
AC:
0
AN:
18518
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.568
Heterozygous variant carriers
0
1
2
3
4
5
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
AF:
0.0000329
AC:
5
AN:
151896
Hom.:
0
Cov.:
29
AF XY:
0.0000404
AC XY:
3
AN XY:
74200
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41366
American (AMR)
AF:
0.0000655
AC:
1
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5154
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10566
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000442
AC:
3
AN:
67934
Other (OTH)
AF:
0.00
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

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

Submissions by phenotype

Progressive myoclonic epilepsy type 3 Uncertain:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
3.3
DANN
Benign
0.57
PhyloP100
-1.0
PromoterAI
-0.0049
Neutral

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: rs886062407; hg19: chr7-66093871; API