chr7-66629086-G-C

Variant names:

• chr7-66629086-G-C
• rs1308286439
• NM_153033.5:c.22G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_153033.5(KCTD7):​c.22G>C​(p.Glu8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000848 in 1,532,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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 2 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=0.1243439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.22G>C	p.Glu8Gln	missense_variant	Exon 1 of 4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.22G>C	p.Glu8Gln	missense_variant	Exon 1 of 5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.22G>C	p.Glu8Gln	missense_variant	Exon 1 of 4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.22G>C		non_coding_transcript_exon_variant	Exon 1 of 13	2		ENSP00000421074.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151920 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000724 AC: 10 AN: 1380580 Hom.: 0 Cov.: 34 AF XY: 0.00000586 AC XY: 4 AN XY: 683148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000308

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151920 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74214

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T;.;.;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.83	T;T;T;T;T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.;N;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.010	.;N;.;N;.;.
REVEL	Benign	0.10
Sift	Benign	0.49	.;T;.;T;.;.
Sift4G	Benign	0.57	.;T;.;T;.;.
Polyphen		0.013	B;.;.;.;.;.
Vest4		0.15, 0.15
MutPred		0.16		Gain of MoRF binding (P = 0.0134);Gain of MoRF binding (P = 0.0134);Gain of MoRF binding (P = 0.0134);Gain of MoRF binding (P = 0.0134);Gain of MoRF binding (P = 0.0134);Gain of MoRF binding (P = 0.0134);
MVP		0.57
ClinPred		0.22	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.32

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: rs1308286439; hg19: chr7-66094073;