22-30399716-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_012429.5(SEC14L2):c.128G>A(p.Arg43Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012429.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC14L2 | NM_012429.5 | c.128G>A | p.Arg43Gln | missense_variant, splice_region_variant | 2/12 | ENST00000615189.5 | |
SEC14L2 | NM_033382.3 | c.128G>A | p.Arg43Gln | missense_variant, splice_region_variant | 2/11 | ||
SEC14L2 | NM_001204204.3 | c.128G>A | p.Arg43Gln | missense_variant, splice_region_variant | 2/10 | ||
SEC14L2 | NM_001291932.2 | c.-33+2546G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC14L2 | ENST00000615189.5 | c.128G>A | p.Arg43Gln | missense_variant, splice_region_variant | 2/12 | 1 | NM_012429.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250448Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135420
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461032Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726814
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The c.128G>A (p.R43Q) alteration is located in exon 2 (coding exon 2) of the SEC14L2 gene. This alteration results from a G to A substitution at nucleotide position 128, causing the arginine (R) at amino acid position 43 to be replaced by a glutamine (Q). 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