16-2702364-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018992.4(KCTD5):c.561C>T(p.Ile187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,613,460 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (49 hom.)
• Consequence: KCTD5 NM_018992.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.546

Genes affected

KCTD5 (HGNC:21423): (potassium channel tetramerization domain containing 5) Enables identical protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005100876).
• BP6: Variant 16-2702364-C-T is Benign according to our data. Variant chr16-2702364-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.546 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD5	NM_018992.4	c.561C>T	p.Ile187=	synonymous_variant	5/6	ENST00000301738.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD5	ENST00000301738.9	c.561C>T	p.Ile187=	synonymous_variant	5/6	1	NM_018992.4	P1
KCTD5	ENST00000564195.1	c.469C>T	p.Arg157Trp	missense_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.00505 AC: 768 AN: 152148 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00539 AC: 1353 AN: 250972 Hom.: 5 AF XY: 0.00529 AC XY: 718 AN XY: 135808

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00776

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.00825

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00703 AC: 10278 AN: 1461194 Hom.: 49 Cov.: 31 AF XY: 0.00686 AC XY: 4990 AN XY: 726918

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00746

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.00806

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.00504 AC: 768 AN: 152266 Hom.: 2 Cov.: 33 AF XY: 0.00502 AC XY: 374 AN XY: 74444

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00765

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00695 Hom.: 1

Bravo AF: 0.00396

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00205 AC: 9

ESP6500EA AF: 0.00744 AC: 64

ExAC AF: 0.00551 AC: 669

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00556

EpiControl AF: 0.00646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

KCTD5: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Benign	6.2
Dann	Uncertain	0.98
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0051	T
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	1.7	N
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Vest4		0.41
MVP		0.81
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs118149302; hg19: chr16-2752365; COSMIC: COSV57064830; COSMIC: COSV57064830;