12-121000906-G-GTT

Position:

• chr12-121000906-G-GTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_022895.3(C12orf43):​c.*3246_*3247insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (43258 hom., cov: 0)
  • Exomes 𝑓: 0.81 (287503 hom.)
• Consequence: C12orf43 NM_022895.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-121000906-G-GTT is Benign according to our data. Variant chr12-121000906-G-GTT is described in ClinVar as [Benign]. Clinvar id is 1249732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf43	NM_022895.3	c.*3246_*3247insAA		3_prime_UTR_variant	6/6	ENST00000288757.7	NP_075046.1
HNF1A	NM_000545.8	c.1769-159_1769-158insTT		intron_variant		ENST00000257555.11	NP_000536.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf43	ENST00000288757.7	c.*3246_*3247insAA		3_prime_UTR_variant	6/6	1	NM_022895.3	ENSP00000288757.5
HNF1A	ENST00000257555.11	c.1769-159_1769-158insTT		intron_variant		1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112621 AN: 151754 Hom.: 43226 Cov.: 0

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.807 AC: 707935 AN: 877384 Hom.: 287503 Cov.: 12 AF XY: 0.809 AC XY: 365902 AN XY: 452540

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.907

Gnomad4 ASJ exome AF: 0.876

Gnomad4 EAS exome AF: 0.894

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.803

GnomAD4 genome AF: 0.742 AC: 112702 AN: 151872 Hom.: 43258 Cov.: 0 AF XY: 0.746 AC XY: 55380 AN XY: 74216

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.799

Alfa AF: 0.752 Hom.: 5328

Bravo AF: 0.739

Asia WGS AF: 0.870 AC: 3026 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3999412; hg19: chr12-121438709;