3-57198400-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_003865.3(HESX1):c.450C>G(p.Asp150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
HESX1
NM_003865.3 missense
NM_003865.3 missense
Scores
2
8
4
Clinical Significance
Conservation
PhyloP100: 3.16
Genes affected
HESX1 (HGNC:4877): (HESX homeobox 1) This gene encodes a conserved homeobox protein that is a transcriptional repressor in the developing forebrain and pituitary gland. Mutations in this gene are associated with septooptic dysplasia, HESX1-related growth hormone deficiency, and combined pituitary hormone deficiency. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a helix (size 15) in uniprot entity HESX1_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_003865.3
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HESX1 | NM_003865.3 | c.450C>G | p.Asp150Glu | missense_variant | 3/4 | ENST00000295934.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HESX1 | ENST00000295934.8 | c.450C>G | p.Asp150Glu | missense_variant | 3/4 | 1 | NM_003865.3 | P1 | |
HESX1 | ENST00000647958.1 | c.450C>G | p.Asp150Glu | missense_variant | 6/7 | P1 | |||
HESX1 | ENST00000473921.2 | c.358-105C>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1441890Hom.: 0 Cov.: 27 AF XY: 0.00000278 AC XY: 2AN XY: 718768
GnomAD4 exome
AF:
AC:
3
AN:
1441890
Hom.:
Cov.:
27
AF XY:
AC XY:
2
AN XY:
718768
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Septo-optic dysplasia sequence Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Moosajee Lab, UCL Institute of Ophthalmology | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
D;D
Vest4
0.56
MutPred
Loss of MoRF binding (P = 0.1225);Loss of MoRF binding (P = 0.1225);
MVP
0.94
MPC
0.32
ClinPred
D
GERP RS
Varity_R
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