rs1329019664

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_175914.5(HNF4A):​c.28G>A​(p.Ala10Thr) variant causes a missense change. 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.

Frequency

Genomes: not found (cov: 32)

Consequence

HNF4A
NM_175914.5 missense

Scores

7
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.27
Variant links:
Genes affected
HNF4A (HGNC:5024): (hepatocyte nuclear factor 4 alpha) The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Apr 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30432746).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNF4ANM_175914.5 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 10 ENST00000316673.9 NP_787110.2 P41235-5F1D8T0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNF4AENST00000316673.9 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 10 1 NM_175914.5 ENSP00000315180.4 P41235-5
HNF4AENST00000457232.5 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 10 1 ENSP00000396216.1 P41235-6
HNF4AENST00000609795.5 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 8 1 ENSP00000476609.1 P41235-7
HNF4AENST00000609262 linkc.-204G>A 5_prime_UTR_variant Exon 1 of 4 1 ENSP00000476310.1 B9VVT8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
21
DANN
Uncertain
0.99
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.51
T;T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Uncertain
0.28
D
PROVEAN
Benign
-0.080
N;.;N
REVEL
Uncertain
0.29
Sift
Benign
0.43
T;.;T
Sift4G
Benign
0.71
T;T;T
Polyphen
1.0, 0.99
.;D;D
Vest4
0.33
MutPred
0.21
Gain of glycosylation at A10 (P = 0.0122);Gain of glycosylation at A10 (P = 0.0122);Gain of glycosylation at A10 (P = 0.0122);
MVP
0.77
ClinPred
0.62
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

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: rs1329019664; hg19: chr20-42984472; COSMIC: COSV99407201; COSMIC: COSV99407201; API