12-120978572-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM2_Supporting
This summary comes from the ClinGen Evidence Repository: The c.-197C>T variant in the HNF1 homeobox A gene, HNF1A, is a single nucleotide variant within the 5' UTR of NM_000545.8. This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting). This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors). Additionally, PP4 cannot be applied as the calculated MODY probability is <50% (internal lab contributors). In summary, c.-197C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 08/11/2023): PM2_Supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA2797727079/MONDO:0015967/017
Frequency
Consequence
NM_000545.8 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.-197C>T | 5_prime_UTR_variant | Exon 1 of 10 | ENST00000257555.11 | NP_000536.6 | ||
HNF1A | NM_001306179.2 | c.-197C>T | 5_prime_UTR_variant | Exon 1 of 10 | NP_001293108.2 | |||
HNF1A | NM_001406915.1 | c.-197C>T | 5_prime_UTR_variant | Exon 1 of 9 | NP_001393844.1 | |||
HNF1A | XM_024449168.2 | c.-197C>T | 5_prime_UTR_variant | Exon 1 of 9 | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555 | c.-197C>T | 5_prime_UTR_variant | Exon 1 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 3
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Monogenic diabetes Uncertain:1
The c.-197C>T variant in the HNF1 homeobox A gene, HNF1A, is a single nucleotide variant within the 5' UTR of NM_000545.8. This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting). This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors). Additionally, PP4 cannot be applied as the calculated MODY probability is <50% (internal lab contributors). In summary, c.-197C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 08/11/2023): PM2_Supporting. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.