12-14770925-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_175054.2(H4C16):c.160G>A(p.Glu54Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 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 Uncertain significance (★).
Frequency
Consequence
NM_175054.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
H4C16 | ENST00000539745.2 | c.160G>A | p.Glu54Lys | missense_variant | Exon 1 of 1 | 6 | NM_175054.2 | ENSP00000443017.1 | ||
H4C16 | ENST00000358064.3 | n.160G>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 1 | ENSP00000350767.3 | ||||
H4C16 | ENST00000540565.1 | n.-132G>A | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251442Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461884Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.160G>A (p.E54K) alteration is located in exon 1 (coding exon 1) of the HIST4H4 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the glutamic acid (E) at amino acid position 54 to be replaced by a lysine (K). 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