chr15-45402430-A-T

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

Scores

5
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14
Variant links:
Genes affected
AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

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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
SPATA5L1NM_024063.3 linkuse as main transcriptc.1A>T p.Met1? start_lost 1/8 ENST00000305560.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFG2BENST00000305560.11 linkuse as main transcriptc.1A>T p.Met1? start_lost 1/81 NM_024063.3 P1Q9BVQ7-1
AFG2BENST00000559860.2 linkuse as main transcriptn.61A>T non_coding_transcript_exon_variant 1/52
AFG2BENST00000531970.5 linkuse as main transcriptc.1A>T p.Met1? start_lost, NMD_transcript_variant 1/82 Q9BVQ7-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000253
AC:
6
AN:
236870
Hom.:
0
AF XY:
0.00000775
AC XY:
1
AN XY:
129024
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000158
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000176
GnomAD4 exome
AF:
0.00000345
AC:
5
AN:
1448536
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
720688
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000119
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000302
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingGeneDxFeb 05, 2018The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.43
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.0087
T;.
Eigen
Benign
0.097
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.98
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Uncertain
0.26
D
MutationTaster
Benign
1.0
D;D
PROVEAN
Benign
-0.98
N;.
REVEL
Uncertain
0.64
Sift
Pathogenic
0.0
D;.
Sift4G
Benign
0.21
T;.
Polyphen
0.82
P;.
Vest4
0.95
MutPred
0.99
Gain of glycosylation at S5 (P = 0.3342);Gain of glycosylation at S5 (P = 0.3342);
MVP
0.68
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.96
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751354951; hg19: chr15-45694628; API