dbSNP rs34544607: KCTD12:p.Thr178Thr (chr13-76885615-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_138444.4(KCTD12):c.534G>C(p.Thr178Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,504,778 control chromosomes in the GnomAD database, including 1,442 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.039 ( 130 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1312 hom. )

Consequence

KCTD12
NM_138444.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.642

Publications

4 publications found

Variant links:

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]

KCTD12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD12	NM_138444.4 link	c.534G>C	p.Thr178Thr	synonymous_variant	Exon 1 of 1	ENST00000377474.4	NP_612453.1	Q96CX2A0A140VJM4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD12	ENST00000377474.4 link	c.534G>C	p.Thr178Thr	synonymous_variant	Exon 1 of 1	6	NM_138444.4	ENSP00000366694.2		Q96CX2

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5913

AN:

152126

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0906

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0425

GnomAD2 exomes

AF:

0.0475

AC:

4912

AN:

103406

AF XY:

0.0511

show subpopulations

Gnomad AFR exome

AF:

0.0578

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.0886

Gnomad EAS exome

AF:

0.000234

Gnomad FIN exome

AF:

0.0371

Gnomad NFE exome

AF:

0.0443

Gnomad OTH exome

AF:

0.0482

GnomAD4 exome

AF:

0.0406

AC:

54894

AN:

1352544

Hom.:

1312

Cov.:

AF XY:

0.0418

AC XY:

27897

AN XY:

666812

show subpopulations

African (AFR)

AF:

0.0444

AC:

1290

AN:

29086

American (AMR)

AF:

0.0204

AC:

588

AN:

28890

Ashkenazi Jewish (ASJ)

AF:

0.0782

AC:

1722

AN:

22010

East Asian (EAS)

AF:

0.000114

AC:

AN:

35150

South Asian (SAS)

AF:

0.0900

AC:

6571

AN:

72988

European-Finnish (FIN)

AF:

0.0292

AC:

995

AN:

34106

Middle Eastern (MID)

AF:

0.0664

AC:

278

AN:

4188

European-Non Finnish (NFE)

AF:

0.0384

AC:

41065

AN:

1069864

Other (OTH)

AF:

0.0423

AC:

2381

AN:

56262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3245

6490

9734

12979

16224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0388

AC:

5913

AN:

152234

Hom.:

130

Cov.:

AF XY:

0.0393

AC XY:

2925

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0423

AC:

1756

AN:

41560

American (AMR)

AF:

0.0267

AC:

408

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0726

AC:

252

AN:

3472

East Asian (EAS)

AF:

0.000583

AC:

AN:

5148

South Asian (SAS)

AF:

0.0907

AC:

438

AN:

4830

European-Finnish (FIN)

AF:

0.0311

AC:

330

AN:

10612

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0370

AC:

2519

AN:

67996

Other (OTH)

AF:

0.0421

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

300

600

900

1200

1500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0419

Hom.:

Bravo

AF:

0.0378

Asia WGS

AF:

0.0370

AC:

127

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs34544607

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over