rs1060499866
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000545.8(HNF1A):c.539C>A(p.Ala180Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
HNF1A
NM_000545.8 missense
NM_000545.8 missense
Scores
8
6
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.61
Genes affected
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
In a domain POU-specific atypical (size 95) in uniprot entity HNF1A_HUMAN there are 52 pathogenic changes around while only 3 benign (95%) in NM_000545.8
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.539C>A | p.Ala180Glu | missense_variant | 3/10 | ENST00000257555.11 | NP_000536.6 | |
HNF1A | NM_001306179.2 | c.539C>A | p.Ala180Glu | missense_variant | 3/10 | NP_001293108.2 | ||
HNF1A | NM_001406915.1 | c.539C>A | p.Ala180Glu | missense_variant | 3/9 | NP_001393844.1 | ||
HNF1A | XM_024449168.2 | c.539C>A | p.Ala180Glu | missense_variant | 3/9 | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.539C>A | p.Ala180Glu | missense_variant | 3/10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461780Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727196
GnomAD4 exome
AF:
AC:
1
AN:
1461780
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
727196
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Pathogenic
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.;.;N;N
REVEL
Pathogenic
Sift
Benign
D;.;.;.;D;D
Sift4G
Uncertain
D;T;T;D;D;D
Polyphen
0.57
.;.;.;.;.;P
Vest4
MutPred
Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.