2-200439236-C-T

Variant summary

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

The NM_001100423.2(SPATS2L):​c.560C>T​(p.Pro187Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
Variant links:
Genes affected
SPATS2L (HGNC:24574): (spermatogenesis associated serine rich 2 like) Enables RNA binding activity. Located in cytosol; nucleolus; and nucleoplasm. Part of protein-containing complex. [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=0.0857918).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPATS2LNM_001100423.2 linkuse as main transcriptc.560C>T p.Pro187Leu missense_variant 7/13 ENST00000409140.8 NP_001093893.1 Q9NUQ6-1A0A024R3V0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPATS2LENST00000409140.8 linkuse as main transcriptc.560C>T p.Pro187Leu missense_variant 7/132 NM_001100423.2 ENSP00000386730.3 Q9NUQ6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461416
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726980
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 24, 2024The c.560C>T (p.P187L) alteration is located in exon 7 (coding exon 5) of the SPATS2L gene. This alteration results from a C to T substitution at nucleotide position 560, causing the proline (P) at amino acid position 187 to be replaced by a leucine (L). 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
0.073
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
21
DANN
Benign
0.86
DEOGEN2
Benign
0.00049
T;T;T;T;T;T;T;.;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.099
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.82
.;.;.;T;.;D;T;T;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.086
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.42
N;N;N;.;N;.;N;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.26
N;N;N;N;N;N;N;.;N
REVEL
Benign
0.073
Sift
Benign
0.68
T;T;T;T;T;T;T;.;T
Sift4G
Benign
0.69
T;T;T;T;T;T;T;T;.
Polyphen
0.0050
B;B;B;.;B;.;B;.;.
Vest4
0.077
MutPred
0.36
Loss of glycosylation at P187 (P = 0.0211);Loss of glycosylation at P187 (P = 0.0211);Loss of glycosylation at P187 (P = 0.0211);.;Loss of glycosylation at P187 (P = 0.0211);Loss of glycosylation at P187 (P = 0.0211);Loss of glycosylation at P187 (P = 0.0211);.;.;
MVP
0.043
MPC
0.85
ClinPred
0.63
D
GERP RS
5.3
Varity_R
0.031
gMVP
0.58

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: rs2084520004; hg19: chr2-201303959; API