chr17-37744584-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_000458.4(HNF1B):āc.301G>Cā(p.Glu101Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000962 in 1,454,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
HNF1B
NM_000458.4 missense
NM_000458.4 missense
Scores
4
6
5
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
HNF1B (HGNC:11630): (HNF1 homeobox B) This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM1
In a domain POU-specific atypical (size 95) in uniprot entity HNF1B_HUMAN there are 46 pathogenic changes around while only 0 benign (100%) in NM_000458.4
PP3
MetaRNN computational evidence supports a deleterious effect, 0.867
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1B | NM_000458.4 | c.301G>C | p.Glu101Gln | missense_variant | 1/9 | ENST00000617811.5 | NP_000449.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1B | ENST00000617811.5 | c.301G>C | p.Glu101Gln | missense_variant | 1/9 | 1 | NM_000458.4 | ENSP00000480291.1 | ||
HNF1B | ENST00000621123.4 | c.301G>C | p.Glu101Gln | missense_variant | 1/9 | 1 | ENSP00000482711.1 | |||
HNF1B | ENST00000613727.4 | c.301G>C | p.Glu101Gln | missense_variant | 1/7 | 1 | ENSP00000477524.1 | |||
HNF1B | ENST00000614313.4 | c.301G>C | p.Glu101Gln | missense_variant | 1/8 | 5 | ENSP00000482529.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000408 AC: 1AN: 245210Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133484
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GnomAD4 exome AF: 0.00000962 AC: 14AN: 1454878Hom.: 0 Cov.: 35 AF XY: 0.00000967 AC XY: 7AN XY: 724090
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 14, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 101 of the HNF1B protein (p.Glu101Gln). This variant is present in population databases (rs121918671, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HNF1B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HNF1B protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.;.;.
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
P;.;.;.;.;.
Vest4
MutPred
Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at