Genetic Variant C12orf43:c.452+136A>G (chr12-121004867-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022895.3(C12orf43):c.452+136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 600,270 control chromosomes in the GnomAD database, including 42,156 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 0.32 ( 8761 hom., cov: 31)

Exomes 𝑓: 0.38 ( 33395 hom. )

Consequence

C12orf43
NM_022895.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.291

Publications

46 publications found

Variant links:

Genes affected

C12orf43 (HGNC:25719): (chromosome 12 open reading frame 43) Predicted to be involved in Spemann organizer formation and negative regulation of Wnt signaling pathway. Predicted to be located in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

C12orf43 links:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022895.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf43	NM_022895.3	MANE Select	c.452+136A>G	intron	N/A	NP_075046.1
C12orf43	NM_001286191.2		c.545+136A>G	intron	N/A	NP_001273120.1	F5H7W8
C12orf43	NM_001286192.2		c.452+136A>G	intron	N/A	NP_001273121.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf43	ENST00000288757.7	TSL:1 MANE Select	c.452+136A>G	intron	N/A	ENSP00000288757.5	Q96C57
C12orf43	ENST00000537817.5	TSL:1	c.545+136A>G	intron	N/A	ENSP00000442224.2	F5H7W8
C12orf43	ENST00000886556.1		c.545+136A>G	intron	N/A	ENSP00000556615.1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48590

AN:

151878

Hom.:

8759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.372

GnomAD4 exome

AF:

0.377

AC:

169116

AN:

448274

Hom.:

33395

AF XY:

0.381

AC XY:

86111

AN XY:

226228

show subpopulations

African (AFR)

AF:

0.140

AC:

1488

AN:

10634

American (AMR)

AF:

0.405

AC:

4543

AN:

11228

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

5914

AN:

11300

East Asian (EAS)

AF:

0.536

AC:

13838

AN:

25796

South Asian (SAS)

AF:

0.509

AC:

9966

AN:

19564

European-Finnish (FIN)

AF:

0.363

AC:

13682

AN:

37686

Middle Eastern (MID)

AF:

0.546

AC:

973

AN:

1782

European-Non Finnish (NFE)

AF:

0.358

AC:

109752

AN:

306558

Other (OTH)

AF:

0.378

AC:

8960

AN:

23726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5293

10585

15878

21170

26463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2070

4140

6210

8280

10350

<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:

0.320

AC:

48590

AN:

151996

Hom.:

8761

Cov.:

AF XY:

0.329

AC XY:

24415

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.145

AC:

6021

AN:

41480

American (AMR)

AF:

0.394

AC:

6023

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

1811

AN:

3466

East Asian (EAS)

AF:

0.490

AC:

2526

AN:

5160

South Asian (SAS)

AF:

0.513

AC:

2465

AN:

4806

European-Finnish (FIN)

AF:

0.384

AC:

4056

AN:

10556

Middle Eastern (MID)

AF:

0.586

AC:

171

AN:

292

European-Non Finnish (NFE)

AF:

0.359

AC:

24369

AN:

67942

Other (OTH)

AF:

0.377

AC:

795

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1624

3248

4871

6495

8119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.348

Hom.:

12884

Bravo

AF:

0.311

Asia WGS

AF:

0.478

AC:

1660

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.3

(source)

DANN

Benign

0.43

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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