12-49494928-T-G

Variant summary

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

The NM_023071.4(SPATS2):​c.452T>G​(p.Leu151Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SPATS2
NM_023071.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.23
Variant links:
Genes affected
SPATS2 (HGNC:18650): (spermatogenesis associated serine rich 2) Enables RNA binding activity. Located in cytosol. [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=0.24864176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATS2NM_023071.4 linkc.452T>G p.Leu151Trp missense_variant Exon 7 of 14 ENST00000552918.6 NP_075559.2 Q86XZ4A0A024R101

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATS2ENST00000552918.6 linkc.452T>G p.Leu151Trp missense_variant Exon 7 of 14 2 NM_023071.4 ENSP00000447947.2 Q86XZ4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152098
Hom.:
0
Cov.:
32
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:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251334
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000979
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461832
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000453
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.452T>G (p.L151W) alteration is located in exon 7 (coding exon 5) of the SPATS2 gene. This alteration results from a T to G substitution at nucleotide position 452, causing the leucine (L) at amino acid position 151 to be replaced by a tryptophan (W). 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
0.12
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
28
DANN
Benign
0.96
DEOGEN2
Benign
0.35
T;T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.86
.;.;D
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Uncertain
2.4
M;M;M
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0070
D;D;D
Sift4G
Uncertain
0.012
D;D;D
Polyphen
0.99
D;D;D
Vest4
0.59
MutPred
0.82
Loss of disorder (P = 0.0533);Loss of disorder (P = 0.0533);Loss of disorder (P = 0.0533);
MVP
0.18
MPC
0.93
ClinPred
0.46
T
GERP RS
5.3
Varity_R
0.21
gMVP
0.34

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: rs538794407; hg19: chr12-49888711; API