chr17-7353587-C-G

Position:

• chr17-7353587-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363642.1(KCTD11):​c.762C>G​(p.Phe254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KCTD11 NM_001363642.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

KCTD11 (HGNC:21302): (potassium channel tetramerization domain containing 11) Enables identical protein binding activity. Predicted to be involved in positive regulation of neuron differentiation. Predicted to act upstream of or within negative regulation of neuroblast proliferation and negative regulation of smoothened signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15064749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD11	NM_001363642.1	c.762C>G	p.Phe254Leu	missense_variant	1/1	ENST00000333751.8
KCTD11	NM_001002914.3	c.645C>G	p.Phe215Leu	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD11	ENST00000333751.8	c.762C>G	p.Phe254Leu	missense_variant	1/1		NM_001363642.1
	ENST00000572417.1	n.276-755G>C		intron_variant, non_coding_transcript_variant		2
KCTD11	ENST00000576980.2	c.645C>G	p.Phe215Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381072 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 678306

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: 9.33e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.66	T
Polyphen		0.030	B;.
MutPred		0.14		Gain of disorder (P = 0.1332);.;
MVP		0.68
MPC		1.8
ClinPred		0.80	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.51

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: rs771992131; hg19: chr17-7256906;