12-121000508-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022895.3(C12orf43):​c.*3645G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 179,720 control chromosomes in the GnomAD database, including 10,655 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 ( 8732 hom., cov: 32)
Exomes 𝑓: 0.34 ( 1923 hom. )

Consequence

C12orf43
NM_022895.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C12orf43NM_022895.3 linkuse as main transcriptc.*3645G>A 3_prime_UTR_variant 6/6 ENST00000288757.7 NP_075046.1
HNF1ANM_000545.8 linkuse as main transcriptc.1769-557C>T intron_variant ENST00000257555.11 NP_000536.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C12orf43ENST00000288757.7 linkuse as main transcriptc.*3645G>A 3_prime_UTR_variant 6/61 NM_022895.3 ENSP00000288757 P2
HNF1AENST00000257555.11 linkuse as main transcriptc.1769-557C>T intron_variant 1 NM_000545.8 ENSP00000257555 P4

Frequencies

GnomAD3 genomes
AF:
0.319
AC:
48533
AN:
151934
Hom.:
8728
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.146
Gnomad AMI
AF:
0.376
Gnomad AMR
AF:
0.393
Gnomad ASJ
AF:
0.507
Gnomad EAS
AF:
0.490
Gnomad SAS
AF:
0.519
Gnomad FIN
AF:
0.385
Gnomad MID
AF:
0.582
Gnomad NFE
AF:
0.358
Gnomad OTH
AF:
0.370
GnomAD4 exome
AF:
0.343
AC:
9484
AN:
27668
Hom.:
1923
Cov.:
0
AF XY:
0.354
AC XY:
4979
AN XY:
14072
show subpopulations
Gnomad4 AFR exome
AF:
0.0912
Gnomad4 AMR exome
AF:
0.382
Gnomad4 ASJ exome
AF:
0.441
Gnomad4 EAS exome
AF:
0.468
Gnomad4 SAS exome
AF:
0.484
Gnomad4 FIN exome
AF:
0.283
Gnomad4 NFE exome
AF:
0.309
Gnomad4 OTH exome
AF:
0.315
GnomAD4 genome
AF:
0.319
AC:
48536
AN:
152052
Hom.:
8732
Cov.:
32
AF XY:
0.328
AC XY:
24398
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.146
Gnomad4 AMR
AF:
0.393
Gnomad4 ASJ
AF:
0.507
Gnomad4 EAS
AF:
0.490
Gnomad4 SAS
AF:
0.518
Gnomad4 FIN
AF:
0.385
Gnomad4 NFE
AF:
0.358
Gnomad4 OTH
AF:
0.375
Alfa
AF:
0.210
Hom.:
511
Bravo
AF:
0.310
Asia WGS
AF:
0.480
AC:
1664
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.011
DANN
Benign
0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1169306; hg19: chr12-121438311; API