chr12-53269676-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_012291.5(ESPL1):c.734C>A(p.Pro245His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P245S) has been classified as Uncertain significance.
Frequency
Consequence
NM_012291.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPL1 | NM_012291.5 | c.734C>A | p.Pro245His | missense_variant | 3/31 | ENST00000257934.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPL1 | ENST00000257934.9 | c.734C>A | p.Pro245His | missense_variant | 3/31 | 5 | NM_012291.5 | P1 | |
ESPL1 | ENST00000552671.5 | c.*665C>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/31 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251372Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135850
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461846Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727226
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2023 | The c.734C>A (p.P245H) alteration is located in exon 3 (coding exon 2) of the ESPL1 gene. This alteration results from a C to A substitution at nucleotide position 734, causing the proline (P) at amino acid position 245 to be replaced by a histidine (H). 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