rs73237446

chr13-76885888-G-Achr13-76885888-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_138444.4(KCTD12):c.261C>T(p.Phe87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,597,208 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0088 (82 hom.)
• Consequence: KCTD12 NM_138444.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.32

Genes affected

KCTD12 (HGNC:14678): (potassium channel tetramerization domain containing 12) Enables identical protein binding activity. Predicted to be involved in protein homooligomerization. Predicted to act upstream of or within regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection. Predicted to be part of receptor complex. Predicted to be active in postsynaptic membrane and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 13-76885888-G-A is Benign according to our data. Variant chr13-76885888-G-A is described in ClinVar as [Benign]. Clinvar id is 789220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.32 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD12	NM_138444.4	c.261C>T	p.Phe87=	synonymous_variant	1/1	ENST00000377474.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD12	ENST00000377474.4	c.261C>T	p.Phe87=	synonymous_variant	1/1		NM_138444.4	P1

Frequencies

GnomAD3 genomes AF: 0.00631 AC: 960 AN: 152244 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00966

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00632 AC: 1427 AN: 225942 Hom.: 14 AF XY: 0.00626 AC XY: 784 AN XY: 125142

Gnomad AFR exome AF: 0.00153

Gnomad AMR exome AF: 0.00519

Gnomad ASJ exome AF: 0.0167

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00116

Gnomad FIN exome AF: 0.00220

Gnomad NFE exome AF: 0.00940

Gnomad OTH exome AF: 0.00716

GnomAD4 exome AF: 0.00880 AC: 12719 AN: 1444846 Hom.: 82 Cov.: 32 AF XY: 0.00852 AC XY: 6124 AN XY: 719160

Gnomad4 AFR exome AF: 0.00231

Gnomad4 AMR exome AF: 0.00542

Gnomad4 ASJ exome AF: 0.0155

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000930

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.00955

GnomAD4 genome AF: 0.00628 AC: 957 AN: 152362 Hom.: 4 Cov.: 33 AF XY: 0.00552 AC XY: 411 AN XY: 74512

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00620

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.00964

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00581 Hom.: 3

Bravo AF: 0.00641

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0112

EpiControl AF: 0.0115

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

Invitae

Jul 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	11
Dann	Benign	0.97

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: rs73237446; hg19: chr13-77460023;