7-66639152-A-G

Position:

• chr7-66639152-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_153033.5(KCTD7):​c.790A>G​(p.Ile264Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.62

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]

ENSG00000284461 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a chain BTB/POZ domain-containing protein KCTD7 (size 288) in uniprot entity KCTD7_HUMAN there are 7 pathogenic changes around while only 2 benign (78%) in NM_153033.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30256587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.790A>G	p.Ile264Val	missense_variant	4/4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.790A>G	p.Ile264Val	missense_variant	4/5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.790A>G	p.Ile264Val	missense_variant	4/4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.397+223A>G		intron_variant		2		ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251340 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135864

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0075	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.6	L;.;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.070	.;.;N;.
REVEL	Benign	0.20
Sift	Benign	0.47	.;.;T;.
Sift4G	Benign	0.56	.;.;T;.
Polyphen		0.80	P;.;.;.
Vest4		0.49
MutPred		0.31		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);.;
MVP		0.76
ClinPred		0.58	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.26

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

Other links and lift over

dbSNP: rs763830869; hg19: chr7-66104139;