chr7-66629016-C-A

Variant summary

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

The ENST00000503687.2(ENSG00000284461):​n.-49C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,321,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

ENSG00000284461
ENST00000503687.2 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203

Publications

0 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=-0.74).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCTD7NM_153033.5 linkc.-49C>A 5_prime_UTR_variant Exon 1 of 4 ENST00000639828.2 NP_694578.1 Q96MP8-1A0A024RDN7
KCTD7NM_001167961.2 linkc.-49C>A 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
ENSG00000284461ENST00000503687.2 linkn.-49C>A non_coding_transcript_exon_variant Exon 1 of 13 2 ENSP00000421074.1 E9PHB8
KCTD7ENST00000639828.2 linkc.-49C>A 5_prime_UTR_variant Exon 1 of 4 2 NM_153033.5 ENSP00000492240.1 Q96MP8-1
ENSG00000284461ENST00000503687.2 linkn.-49C>A 5_prime_UTR_variant Exon 1 of 13 2 ENSP00000421074.1 E9PHB8

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
7.56e-7
AC:
1
AN:
1321944
Hom.:
0
Cov.:
27
AF XY:
0.00000153
AC XY:
1
AN XY:
652064
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
26610
American (AMR)
AF:
0.00
AC:
0
AN:
27648
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22724
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27710
South Asian (SAS)
AF:
0.00
AC:
0
AN:
73158
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44812
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4502
European-Non Finnish (NFE)
AF:
9.61e-7
AC:
1
AN:
1040796
Other (OTH)
AF:
0.00
AC:
0
AN:
53984
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
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.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
6.8
DANN
Benign
0.54
PhyloP100
0.20
PromoterAI
-0.072
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0

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: rs374505432; hg19: chr7-66094003; API