12-121001041-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022895.3(C12orf43):c.*3112A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,611,356 control chromosomes in the GnomAD database, including 111,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8658 hom., cov: 32)

Exomes 𝑓: 0.37 ( 102821 hom. )

Consequence

C12orf43
NM_022895.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0600

Publications

70 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:

HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

HNF1A Gene-Disease associations (from GenCC):

monogenic diabetes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
type 1 diabetes mellitus 20
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
diabetes mellitus, noninsulin-dependent
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
maturity-onset diabetes of the young type 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hyperinsulinism due to HNF1A deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonpapillary renal cell carcinoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

HNF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-121001041-T-C is Benign according to our data. Variant chr12-121001041-T-C is described in ClinVar as Benign. ClinVar VariationId is 673537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf43	NM_022895.3 link	c.*3112A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000288757.7	NP_075046.1
HNF1A	NM_000545.8 link	c.1769-24T>C		intron_variant	Intron 9 of 9	ENST00000257555.11	NP_000536.6	P20823E0YMI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf43	ENST00000288757.7 link	c.*3112A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_022895.3	ENSP00000288757.5		Q96C57
HNF1A	ENST00000257555.11 link	c.1769-24T>C		intron_variant	Intron 9 of 9	1	NM_000545.8	ENSP00000257555.5		A0A0A0MQU7

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48329

AN:

151914

Hom.:

8654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.574

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.368

GnomAD2 exomes

AF:

0.392

AC:

96664

AN:

246892

AF XY:

0.403

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.369

AC:

539129

AN:

1459324

Hom.:

102821

Cov.:

AF XY:

0.375

AC XY:

272574

AN XY:

725964

show subpopulations

African (AFR)

AF:

0.137

AC:

4593

AN:

33474

American (AMR)

AF:

0.405

AC:

18096

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

13314

AN:

26132

East Asian (EAS)

AF:

0.526

AC:

20873

AN:

39678

South Asian (SAS)

AF:

0.520

AC:

44807

AN:

86228

European-Finnish (FIN)

AF:

0.364

AC:

18750

AN:

51512

Middle Eastern (MID)

AF:

0.550

AC:

3171

AN:

5768

European-Non Finnish (NFE)

AF:

0.353

AC:

392650

AN:

1111502

Other (OTH)

AF:

0.379

AC:

22875

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

19663

39326

58988

78651

98314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12600

25200

37800

50400

63000

<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:

0.318

AC:

48332

AN:

152032

Hom.:

8658

Cov.:

AF XY:

0.327

AC XY:

24304

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.146

AC:

6047

AN:

41506

American (AMR)

AF:

0.392

AC:

5992

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1758

AN:

3470

East Asian (EAS)

AF:

0.490

AC:

2525

AN:

5150

South Asian (SAS)

AF:

0.514

AC:

2483

AN:

4828

European-Finnish (FIN)

AF:

0.385

AC:

4076

AN:

10580

Middle Eastern (MID)

AF:

0.562

AC:

163

AN:

290

European-Non Finnish (NFE)

AF:

0.356

AC:

24154

AN:

67904

Other (OTH)

AF:

0.373

AC:

789

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1610

3220

4831

6441

8051

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:

0.357

Hom.:

44569

Bravo

AF:

0.309

Asia WGS

AF:

0.482

AC:

1673

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.4

(source)

DANN

Benign

0.75

PhyloP100

0.060

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over