Genetic Variant NM_138444.4:c.*85C>T (chr13-76885086-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_138444.4(KCTD12):c.*85C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,481,002 control chromosomes in the GnomAD database, including 202 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 0.011 ( 14 hom., cov: 32)

Exomes 𝑓: 0.013 ( 188 hom. )

Consequence

KCTD12
NM_138444.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.159

Publications

2 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:

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new If you want to explore the variant's impact on the transcript NM_138444.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.011 (1680/152202) while in subpopulation SAS AF = 0.0293 (141/4812). AF 95% confidence interval is 0.0254. There are 14 homozygotes in GnomAd4. There are 853 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD12	NM_138444.4	MANE Select	c.*85C>T		3_prime_UTR	Exon 1 of 1	NP_612453.1	Q96CX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD12	ENST00000377474.4	TSL:6 MANE Select	c.*85C>T		3_prime_UTR	Exon 1 of 1	ENSP00000366694.2	Q96CX2

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1678

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00656

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0235

GnomAD4 exome

AF:

0.0134

AC:

17829

AN:

1328800

Hom.:

188

Cov.:

AF XY:

0.0140

AC XY:

9135

AN XY:

654464

show subpopulations

African (AFR)

AF:

0.00358

AC:

109

AN:

30456

American (AMR)

AF:

0.0104

AC:

367

AN:

35148

Ashkenazi Jewish (ASJ)

AF:

0.0148

AC:

304

AN:

20586

East Asian (EAS)

AF:

0.00257

AC:

AN:

38536

South Asian (SAS)

AF:

0.0297

AC:

2117

AN:

71370

European-Finnish (FIN)

AF:

0.0102

AC:

473

AN:

46196

Middle Eastern (MID)

AF:

0.0410

AC:

169

AN:

4122

European-Non Finnish (NFE)

AF:

0.0130

AC:

13324

AN:

1027318

Other (OTH)

AF:

0.0157

AC:

867

AN:

55068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

894

1788

2682

3576

4470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0110

AC:

1680

AN:

152202

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

853

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00349

AC:

145

AN:

41532

American (AMR)

AF:

0.0157

AC:

240

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3470

East Asian (EAS)

AF:

0.00658

AC:

AN:

5170

South Asian (SAS)

AF:

0.0293

AC:

141

AN:

4812

European-Finnish (FIN)

AF:

0.0108

AC:

115

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0131

AC:

889

AN:

67994

Other (OTH)

AF:

0.0227

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

(source)

DANN

Benign

0.72

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over