1-52633558-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001042693.3(SHISAL2A):c.65C>T(p.Pro22Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,610,444 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
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SHISAL2A
NM_001042693.3 missense
NM_001042693.3 missense
Scores
9
6
3
Clinical Significance
Conservation
PhyloP100: 5.73
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.796
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHISAL2A | NM_001042693.3 | c.65C>T | p.Pro22Leu | missense_variant | 1/3 | ENST00000517870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHISAL2A | ENST00000517870.2 | c.65C>T | p.Pro22Leu | missense_variant | 1/3 | 1 | NM_001042693.3 | P1 | |
SHISAL2A | ENST00000401050.7 | n.165C>T | non_coding_transcript_exon_variant | 1/6 | 1 | ||||
SHISAL2A | ENST00000440303.5 | n.215C>T | non_coding_transcript_exon_variant | 1/5 | 2 | ||||
SHISAL2A | ENST00000424164.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000294 AC: 7AN: 238246Hom.: 0 AF XY: 0.0000382 AC XY: 5AN XY: 130792
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1458124Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 725430
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 05, 2023 | The c.65C>T (p.P22L) alteration is located in exon 1 (coding exon 1) of the FAM159A gene. This alteration results from a C to T substitution at nucleotide position 65, causing the proline (P) at amino acid position 22 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0064);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at