chr15-45402739-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024063.3(SPATA5L1):ā€‹c.310T>Cā€‹(p.Cys104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,566,928 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.000040 ( 0 hom. )

Consequence

SPATA5L1
NM_024063.3 missense

Scores

7
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPATA5L1NM_024063.3 linkuse as main transcriptc.310T>C p.Cys104Arg missense_variant 1/8 ENST00000305560.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFG2BENST00000305560.11 linkuse as main transcriptc.310T>C p.Cys104Arg missense_variant 1/81 NM_024063.3 P1Q9BVQ7-1
AFG2BENST00000559860.2 linkuse as main transcriptn.370T>C non_coding_transcript_exon_variant 1/52
AFG2BENST00000531970.5 linkuse as main transcriptc.310T>C p.Cys104Arg missense_variant, NMD_transcript_variant 1/82 Q9BVQ7-2

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000597
AC:
1
AN:
167640
Hom.:
0
AF XY:
0.0000107
AC XY:
1
AN XY:
93076
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:
0.0000143
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000396
AC:
56
AN:
1414720
Hom.:
0
Cov.:
34
AF XY:
0.0000428
AC XY:
30
AN XY:
701264
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:
0.0000466
Gnomad4 OTH exome
AF:
0.0000849
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152208
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000360
Hom.:
0
Bravo
AF:
0.0000151

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 testingCeGaT Center for Human Genetics TuebingenSep 01, 2023AFG2B: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.30
CADD
Benign
23
DANN
Benign
0.96
DEOGEN2
Benign
0.016
T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.54
T;T
M_CAP
Pathogenic
0.39
D
MetaRNN
Pathogenic
0.80
D;D
MetaSVM
Uncertain
0.72
D
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.0
D;.
REVEL
Pathogenic
0.74
Sift
Benign
0.35
T;.
Sift4G
Benign
0.42
T;.
Polyphen
0.99
D;.
Vest4
0.69
MutPred
0.43
Gain of MoRF binding (P = 0.0027);Gain of MoRF binding (P = 0.0027);
MVP
0.87
MPC
1.6
ClinPred
0.92
D
GERP RS
5.0
Varity_R
0.72
gMVP
0.92

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: rs989269379; hg19: chr15-45694937; API