chr15-45402642-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PS1_ModeratePM2BP4

The NM_024063.3(SPATA5L1):​c.213T>G​(p.Phe71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,579,296 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000058 ( 1 hom. )

Consequence

SPATA5L1
NM_024063.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.410
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.

PS1
Transcript NM_024063.3 (SPATA5L1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28502473).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPATA5L1NM_024063.3 linkuse as main transcriptc.213T>G p.Phe71Leu missense_variant 1/8 ENST00000305560.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFG2BENST00000305560.11 linkuse as main transcriptc.213T>G p.Phe71Leu missense_variant 1/81 NM_024063.3 P1Q9BVQ7-1
AFG2BENST00000559860.2 linkuse as main transcriptn.273T>G non_coding_transcript_exon_variant 1/52
AFG2BENST00000531970.5 linkuse as main transcriptc.213T>G p.Phe71Leu missense_variant, NMD_transcript_variant 1/82 Q9BVQ7-2

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152140
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000543
AC:
10
AN:
184116
Hom.:
0
AF XY:
0.0000489
AC XY:
5
AN XY:
102252
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000134
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:
0.0000761
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000582
AC:
83
AN:
1427040
Hom.:
1
Cov.:
34
AF XY:
0.0000678
AC XY:
48
AN XY:
708066
show subpopulations
Gnomad4 AFR exome
AF:
0.000556
Gnomad4 AMR exome
AF:
0.0000972
Gnomad4 ASJ exome
AF:
0.0000393
Gnomad4 EAS exome
AF:
0.0000265
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000409
Gnomad4 OTH exome
AF:
0.000186
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000305
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000258
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023AFG2B: PM2, PM3:Supporting, PP3 -
Neurodevelopmental disorder with hearing loss and spasticity Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInstitute of Medical Genetics and Applied Genomics, University Hospital TübingenMay 12, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Uncertain
0.050
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.0050
T;.
Eigen
Benign
-0.046
Eigen_PC
Benign
-0.081
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.77
T;T
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.4
N;.
REVEL
Uncertain
0.48
Sift
Benign
0.46
T;.
Sift4G
Benign
0.16
T;.
Polyphen
0.98
D;.
Vest4
0.57
MutPred
0.32
Gain of disorder (P = 0.0412);Gain of disorder (P = 0.0412);
MVP
0.96
MPC
1.4
ClinPred
0.24
T
GERP RS
-0.0088
Varity_R
0.16
gMVP
0.75

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: rs776678464; hg19: chr15-45694840; API