21-25769203-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_002040.4(GABPA):c.1336G>T(p.Ala446Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,601,738 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_002040.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABPA | NM_002040.4 | c.1336G>T | p.Ala446Ser | missense_variant | 10/10 | ENST00000400075.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABPA | ENST00000400075.4 | c.1336G>T | p.Ala446Ser | missense_variant | 10/10 | 1 | NM_002040.4 | P1 | |
GABPA | ENST00000354828.7 | c.1336G>T | p.Ala446Ser | missense_variant | 10/10 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249224Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135016
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1449634Hom.: 0 Cov.: 27 AF XY: 0.00000554 AC XY: 4AN XY: 721868
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2023 | The c.1336G>T (p.A446S) alteration is located in exon 10 (coding exon 9) of the GABPA gene. This alteration results from a G to T substitution at nucleotide position 1336, causing the alanine (A) at amino acid position 446 to be replaced by a serine (S). 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