11-78017034-C-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_023930.4(KCTD14):c.327G>T(p.Glu109Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
KCTD14
NM_023930.4 missense
NM_023930.4 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 0.305
Genes affected
KCTD14 (HGNC:23295): (potassium channel tetramerization domain containing 14) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]
NDUFC2-KCTD14 (HGNC:42956): (NDUFC2-KCTD14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NDUFC2 (NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa) and KCTD14 (potassium channel tetramerisation domain containing 14) genes on chromosome 11. The read-through transcripts share sequence identity with the upstream gene product and one variant has a frameshifted C-terminal region derived from the downstream gene exons. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.966
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCTD14 | NM_023930.4 | c.327G>T | p.Glu109Asp | missense_variant | 2/2 | ENST00000353172.6 | NP_076419.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCTD14 | ENST00000353172.6 | c.327G>T | p.Glu109Asp | missense_variant | 2/2 | 1 | NM_023930.4 | ENSP00000316482.5 | ||
KCTD14 | ENST00000533144.1 | c.237G>T | p.Glu79Asp | missense_variant | 3/3 | 1 | ENSP00000431155.1 | |||
NDUFC2-KCTD14 | ENST00000528251.1 | c.*202G>T | 3_prime_UTR_variant | 2/2 | 4 | ENSP00000435967.1 | ||||
NDUFC2-KCTD14 | ENST00000530054.1 | c.*202G>T | downstream_gene_variant | 2 | ENSP00000432614.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251396Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135868
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727248
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2024 | The c.327G>T (p.E109D) alteration is located in exon 2 (coding exon 2) of the KCTD14 gene. This alteration results from a G to T substitution at nucleotide position 327, causing the glutamic acid (E) at amino acid position 109 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of helix (P = 0.2294);.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at