chr2-200467307-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001100423.2(SPATS2L):​c.865C>T​(p.Arg289Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,192 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

11
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPATS2LNM_001100423.2 linkuse as main transcriptc.865C>T p.Arg289Cys missense_variant 10/13 ENST00000409140.8
LOC101927741XR_007088047.1 linkuse as main transcriptn.569+8796G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPATS2LENST00000409140.8 linkuse as main transcriptc.865C>T p.Arg289Cys missense_variant 10/132 NM_001100423.2 P1Q9NUQ6-1
ENST00000655656.1 linkuse as main transcriptn.566+8796G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461192
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726928
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsFeb 27, 2024The c.865C>T (p.R289C) alteration is located in exon 10 (coding exon 8) of the SPATS2L gene. This alteration results from a C to T substitution at nucleotide position 865, causing the arginine (R) at amino acid position 289 to be replaced by a cysteine (C). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.42
T;T;T;T;T;.;T;T;.;.;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.66
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.98
.;.;.;D;.;D;D;D;D;D;D
M_CAP
Benign
0.0067
T
MetaRNN
Pathogenic
0.91
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Uncertain
2.7
M;M;M;.;M;.;M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-7.5
D;D;D;D;D;D;D;D;.;D;D
REVEL
Uncertain
0.51
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;.;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;.;D
Polyphen
1.0
D;D;D;.;D;D;D;.;.;.;.
Vest4
0.90
MutPred
0.80
Loss of MoRF binding (P = 0.0209);Loss of MoRF binding (P = 0.0209);Loss of MoRF binding (P = 0.0209);.;Loss of MoRF binding (P = 0.0209);.;Loss of MoRF binding (P = 0.0209);.;.;.;.;
MVP
0.40
MPC
1.1
ClinPred
1.0
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.79
gMVP
0.96

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: rs2086669559; hg19: chr2-201332030; COSMIC: COSV62350574; COSMIC: COSV62350574; API