NM_003865.3:c.77T>C
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_003865.3(HESX1):āc.77T>Cā(p.Ile26Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
HESX1
NM_003865.3 missense
NM_003865.3 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 6.71
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96
PP5
Variant 3-57199842-A-G is Pathogenic according to our data. Variant chr3-57199842-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 7695.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HESX1 | ENST00000295934.8 | c.77T>C | p.Ile26Thr | missense_variant | Exon 1 of 4 | 1 | NM_003865.3 | ENSP00000295934.3 | ||
HESX1 | ENST00000647958.1 | c.77T>C | p.Ile26Thr | missense_variant | Exon 4 of 7 | ENSP00000498190.1 | ||||
HESX1 | ENST00000473921.2 | c.77T>C | p.Ile26Thr | missense_variant | Exon 1 of 3 | 5 | ENSP00000418918.1 | |||
HESX1 | ENST00000495160.2 | c.77T>C | p.Ile26Thr | missense_variant | Exon 2 of 3 | 3 | ENSP00000419615.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727234
GnomAD4 exome
AF:
AC:
1
AN:
1461856
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727234
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PITUITARY HORMONE DEFICIENCY, COMBINED, 5 Pathogenic:1
Oct 01, 2003
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;D
Sift4G
Uncertain
.;D;D;D
Polyphen
D;D;.;.
Vest4
0.93, 0.99
MutPred
Loss of stability (P = 0.0105);Loss of stability (P = 0.0105);Loss of stability (P = 0.0105);Loss of stability (P = 0.0105);
MVP
0.99
MPC
0.36
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