chr15-45402676-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024063.3(SPATA5L1):​c.247G>A​(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SPATA5L1
NM_024063.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.541
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.085867256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPATA5L1NM_024063.3 linkuse as main transcriptc.247G>A p.Ala83Thr missense_variant 1/8 ENST00000305560.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFG2BENST00000305560.11 linkuse as main transcriptc.247G>A p.Ala83Thr missense_variant 1/81 NM_024063.3 P1Q9BVQ7-1
AFG2BENST00000559860.2 linkuse as main transcriptn.307G>A non_coding_transcript_exon_variant 1/52
AFG2BENST00000531970.5 linkuse as main transcriptc.247G>A p.Ala83Thr missense_variant, NMD_transcript_variant 1/82 Q9BVQ7-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000552
AC:
1
AN:
181308
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
100752
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000129
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.02e-7
AC:
1
AN:
1424210
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
706566
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.10e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2021The c.247G>A (p.A83T) alteration is located in exon 1 (coding exon 1) of the SPATA5L1 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the alanine (A) at amino acid position 83 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.017
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
8.2
DANN
Benign
0.90
DEOGEN2
Benign
0.0072
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.56
T;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.086
T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.3
L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.59
N;.
REVEL
Benign
0.17
Sift
Benign
0.40
T;.
Sift4G
Benign
0.38
T;.
Polyphen
0.0
B;.
Vest4
0.029
MutPred
0.21
Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP
0.61
MPC
0.92
ClinPred
0.055
T
GERP RS
-2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.050
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1381036275; hg19: chr15-45694874; API