rs73237446

Variant names:

• chr13-76885888-G-A
• rs73237446
• NM_138444.4:c.261C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-76885888-G-A
• chr13-76885888-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_138444.4(KCTD12):​c.261C>T​(p.Phe87Phe) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.32
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -15 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 VariationId is 789220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.32 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138444.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD12	NM_138444.4	MANE Select	c.261C>T	p.Phe87Phe	synonymous	Exon 1 of 1	NP_612453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD12	ENST00000377474.4	TSL:6 MANE Select	c.261C>T	p.Phe87Phe	synonymous	Exon 1 of 1	ENSP00000366694.2

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

GnomAD2 exomes AF: 0.00632 AC: 1427 AN: 225942 AF XY: 0.00626

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 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

African (AFR) AF: 0.00231 AC: 77 AN: 33380

American (AMR) AF: 0.00542 AC: 241 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 405 AN: 26094

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39594

South Asian (SAS) AF: 0.000930 AC: 80 AN: 85998

European-Finnish (FIN) AF: 0.00251 AC: 95 AN: 37886

Middle Eastern (MID) AF: 0.0177 AC: 102 AN: 5766

European-Non Finnish (NFE) AF: 0.0100 AC: 11143 AN: 1111400

Other (OTH) AF: 0.00955 AC: 575 AN: 60226

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

African (AFR) AF: 0.00142 AC: 59 AN: 41590

American (AMR) AF: 0.00620 AC: 95 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10630

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00964 AC: 656 AN: 68024

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00630 Hom.: 4

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73237446; hg19: chr13-77460023;