chr15-45402430-A-T
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_024063.3(SPATA5L1):c.1A>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000345 in 1,448,536 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: not found (cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
SPATA5L1
NM_024063.3 start_lost
NM_024063.3 start_lost
Scores
5
4
7
Clinical Significance
Conservation
PhyloP100: 4.14
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPATA5L1 | NM_024063.3 | c.1A>T | p.Met1? | start_lost | 1/8 | ENST00000305560.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG2B | ENST00000305560.11 | c.1A>T | p.Met1? | start_lost | 1/8 | 1 | NM_024063.3 | P1 | |
AFG2B | ENST00000559860.2 | n.61A>T | non_coding_transcript_exon_variant | 1/5 | 2 | ||||
AFG2B | ENST00000531970.5 | c.1A>T | p.Met1? | start_lost, NMD_transcript_variant | 1/8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000253 AC: 6AN: 236870Hom.: 0 AF XY: 0.00000775 AC XY: 1AN XY: 129024
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GnomAD4 exome AF: 0.00000345 AC: 5AN: 1448536Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1AN XY: 720688
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2018 | The c.1 A>T variant in the SPATA5L1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is observed in 5/30716 (0.0163%) alleles from individuals of Latino background, and 6/233090 total alleles in large population cohorts (Lek et al., 2016). As this variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. We interpret c.1 A>T as a variant of uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Benign
T;.
Polyphen
P;.
Vest4
MutPred
Gain of glycosylation at S5 (P = 0.3342);Gain of glycosylation at S5 (P = 0.3342);
MVP
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