2-200419490-G-A

Variant summary

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

The NM_001100423.2(SPATS2L):​c.439G>A​(p.Val147Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
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=0.11801419).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPATS2LNM_001100423.2 linkuse as main transcriptc.439G>A p.Val147Ile missense_variant 6/13 ENST00000409140.8 NP_001093893.1
LOC101927741XR_007088047.1 linkuse as main transcriptn.911-7982C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPATS2LENST00000409140.8 linkuse as main transcriptc.439G>A p.Val147Ile missense_variant 6/132 NM_001100423.2 ENSP00000386730 P1Q9NUQ6-1
ENST00000655656.1 linkuse as main transcriptn.814+9933C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247494
Hom.:
0
AF XY:
0.00000744
AC XY:
1
AN XY:
134492
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461528
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727042
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227

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 GeneticsJul 11, 2023The c.439G>A (p.V147I) alteration is located in exon 6 (coding exon 4) of the SPATS2L gene. This alteration results from a G to A substitution at nucleotide position 439, causing the valine (V) at amino acid position 147 to be replaced by an isoleucine (I). 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
0.065
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.00023
T;T;T;T;T;.;T;T;T;T;.;.;.;.;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.78
.;.;.;T;.;T;T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.12
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N;N;.;N;N;.;.;N;.;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.13
N;N;N;N;N;N;N;N;N;N;.;N;N;N;N
REVEL
Benign
0.065
Sift
Benign
0.38
T;T;T;T;T;T;T;T;T;T;.;T;T;T;T
Sift4G
Benign
0.26
T;T;T;T;T;T;T;T;T;T;T;.;D;T;T
Polyphen
0.0010
B;B;B;.;B;B;.;.;B;.;.;.;.;.;.
Vest4
0.038
MutPred
0.66
Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);.;Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);.;.;Gain of ubiquitination at K142 (P = 0.1132);Gain of ubiquitination at K142 (P = 0.1132);.;
MVP
0.043
MPC
0.22
ClinPred
0.055
T
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.021
gMVP
0.22

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: rs1216051998; hg19: chr2-201284213; API