7-66638349-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4BP6_ModerateBP7

The NM_153033.5(KCTD7):​c.411C>T​(p.Leu137Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,614,132 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: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

KCTD7
NM_153033.5 synonymous

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.961
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.09).
BP6
Variant 7-66638349-C-T is Benign according to our data. Variant chr7-66638349-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 469105.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.961 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCTD7NM_153033.5 linkc.411C>T p.Leu137Leu synonymous_variant Exon 3 of 4 ENST00000639828.2 NP_694578.1 Q96MP8-1A0A024RDN7
KCTD7NM_001167961.2 linkc.411C>T p.Leu137Leu synonymous_variant Exon 3 of 5 NP_001161433.1 Q96MP8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCTD7ENST00000639828.2 linkc.411C>T p.Leu137Leu synonymous_variant Exon 3 of 4 2 NM_153033.5 ENSP00000492240.1 Q96MP8-1
ENSG00000284461ENST00000503687.2 linkn.241C>T non_coding_transcript_exon_variant Exon 2 of 13 2 ENSP00000421074.1 E9PHB8

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152242
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251462
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000766
AC:
112
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.0000839
AC XY:
61
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000926
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000567

ClinVar

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

Submissions by phenotype

Progressive myoclonic epilepsy type 3 Benign:1
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.090
CADD
Benign
5.5
DANN
Uncertain
0.98

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: rs374072904; hg19: chr7-66103336; COSMIC: COSV99299084; COSMIC: COSV99299084; API