14-74494111-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_194279.4(ISCA2):c.133G>A(p.Ala45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,577,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_194279.4 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 |
---|---|---|---|---|---|---|---|
ISCA2 | NM_194279.4 | c.133G>A | p.Ala45Thr | missense_variant | 2/4 | ENST00000556816.6 | |
ISCA2 | NM_001272007.2 | c.133G>A | p.Ala45Thr | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ISCA2 | ENST00000556816.6 | c.133G>A | p.Ala45Thr | missense_variant | 2/4 | 1 | NM_194279.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000523 AC: 1AN: 191238Hom.: 0 AF XY: 0.00000959 AC XY: 1AN XY: 104244
GnomAD4 exome AF: 0.0000260 AC: 37AN: 1425076Hom.: 0 Cov.: 31 AF XY: 0.0000184 AC XY: 13AN XY: 706278
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.133G>A (p.A45T) alteration is located in exon 2 (coding exon 2) of the ISCA2 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the alanine (A) at amino acid position 45 to be replaced by a threonine (T). 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