NM_000545.8:c.1460G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_000545.8(HNF1A):​c.1460G>C​(p.Ser487Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S487N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HNF1A
NM_000545.8 missense

Scores

2
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05
Variant links:
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr12-120997624-G-A is described in Lovd as [Pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.2867908).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNF1ANM_000545.8 linkc.1460G>C p.Ser487Thr missense_variant Exon 7 of 10 ENST00000257555.11 NP_000536.6 P20823E0YMI7
HNF1ANM_001306179.2 linkc.1460G>C p.Ser487Thr missense_variant Exon 7 of 10 NP_001293108.2 P20823E0YMI7
HNF1AXM_024449168.2 linkc.1460G>C p.Ser487Thr missense_variant Exon 7 of 9 XP_024304936.1
HNF1ANM_001406915.1 linkc.1309+882G>C intron_variant Intron 6 of 8 NP_001393844.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNF1AENST00000257555.11 linkc.1460G>C p.Ser487Thr missense_variant Exon 7 of 10 1 NM_000545.8 ENSP00000257555.5 A0A0A0MQU7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
42
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.58
.;D;D;.;T;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.85
T;D;D;D;D;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.29
T;T;T;T;T;T
MetaSVM
Pathogenic
0.90
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.3
N;.;.;.;N;N
REVEL
Uncertain
0.54
Sift
Uncertain
0.021
D;.;.;.;D;D
Sift4G
Benign
0.37
T;T;D;D;T;T
Polyphen
0.10
.;.;.;.;.;B
Vest4
0.49
MutPred
0.42
Loss of glycosylation at S487 (P = 0.0874);Loss of glycosylation at S487 (P = 0.0874);.;.;Loss of glycosylation at S487 (P = 0.0874);Loss of glycosylation at S487 (P = 0.0874);
MVP
0.85
MPC
0.14
ClinPred
0.46
T
GERP RS
3.5
gMVP
0.75

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: rs2464196; hg19: chr12-121435427; COSMIC: COSV105084758; COSMIC: COSV105084758; API