chr18-26455686-TTTTG-T

Position:

• chr18-26455686-TTTTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001142730.3(KCTD1):​c.*53_*56del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,609,596 control chromosomes in the GnomAD database, including 19,187 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1638 hom., cov: 28)
  • Exomes 𝑓: 0.15 (17549 hom.)
• Consequence: KCTD1 NM_001142730.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

Genes affected

KCTD1 (HGNC:18249): (potassium channel tetramerization domain containing 1) This gene encodes a protein containing a BTB (Broad-complex, tramtrack and bric a brac), also known as a POZ (POxvirus and zinc finger) protein-protein interaction domain. The encoded protein negatively regulates the AP-2 family of transcription factors and the Wnt signaling pathway. A mechanism for the modulation of Wnt signaling has been proposed in which the encoded protein enhances ubiquitination and degradation of the beta-catenin protein. Mutations in this gene have been identified in Scalp-ear-nipple (SEN) syndrome. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 18-26455686-TTTTG-T is Benign according to our data. Variant chr18-26455686-TTTTG-T is described in ClinVar as [Benign]. Clinvar id is 1236096.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD1	NM_001142730.3	c.*53_*56del		3_prime_UTR_variant	5/5	ENST00000580059.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD1	ENST00000580059.7	c.*53_*56del		3_prime_UTR_variant	5/5	3	NM_001142730.3	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20953 AN: 151986 Hom.: 1638 Cov.: 28

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.148 AC: 215133 AN: 1457492 Hom.: 17549 AF XY: 0.145 AC XY: 105335 AN XY: 725090

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0717

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.00433

Gnomad4 SAS exome AF: 0.0477

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.138 AC: 20958 AN: 152104 Hom.: 1638 Cov.: 28 AF XY: 0.136 AC XY: 10128 AN XY: 74352

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0894 Hom.: 118

Bravo AF: 0.127

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs146107679; hg19: chr18-24035650;