chr1-999129-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021170.4(HES4):c.596G>T(p.Arg199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,065,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021170.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HES4 | NM_021170.4 | c.596G>T | p.Arg199Leu | missense_variant | 4/4 | ENST00000304952.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HES4 | ENST00000304952.11 | c.596G>T | p.Arg199Leu | missense_variant | 4/4 | 1 | NM_021170.4 | P1 | |
HES4 | ENST00000428771.6 | c.674G>T | p.Arg225Leu | missense_variant | 3/3 | 2 | |||
HES4 | ENST00000484667.2 | c.500G>T | p.Arg167Leu | missense_variant | 3/3 | 3 | |||
HES4 | ENST00000481869.1 | n.875G>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000188 AC: 2AN: 1065154Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 503378
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.674G>T (p.R225L) alteration is located in exon 3 (coding exon 3) of the HES4 gene. This alteration results from a G to T substitution at nucleotide position 674, causing the arginine (R) at amino acid position 225 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.