2-200469956-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.1000G>A​(p.Ala334Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,612,298 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 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11
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=0.17268527).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPATS2LNM_001100423.2 linkuse as main transcriptc.1000G>A p.Ala334Thr missense_variant 11/13 ENST00000409140.8 NP_001093893.1
LOC101927741XR_007088047.1 linkuse as main transcriptn.569+6147C>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.1000G>A p.Ala334Thr missense_variant 11/132 NM_001100423.2 ENSP00000386730 P1Q9NUQ6-1
ENST00000655656.1 linkuse as main transcriptn.566+6147C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152230
Hom.:
0
Cov.:
33
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000528
AC:
13
AN:
246210
Hom.:
0
AF XY:
0.0000525
AC XY:
7
AN XY:
133358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000467
Gnomad NFE exome
AF:
0.000107
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000507
AC:
74
AN:
1460068
Hom.:
0
Cov.:
30
AF XY:
0.0000455
AC XY:
33
AN XY:
726054
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:
0.000150
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152230
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000189
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000579
AC:
7

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 29, 2021The c.1000G>A (p.A334T) alteration is located in exon 11 (coding exon 9) of the SPATS2L gene. This alteration results from a G to A substitution at nucleotide position 1000, causing the alanine (A) at amino acid position 334 to be replaced by a threonine (T). 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
Uncertain
0.37
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0025
T;T;T;T;T;.;T;T;.;.
Eigen
Benign
-0.023
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
.;.;.;D;.;D;D;D;D;D
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.15
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.7
L;L;L;.;L;.;L;.;.;.
MutationTaster
Benign
0.73
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.50
N;N;N;N;N;N;N;N;.;N
REVEL
Benign
0.10
Sift
Benign
0.19
T;T;T;T;T;T;T;T;.;T
Sift4G
Benign
0.61
T;T;T;T;T;T;T;D;T;.
Polyphen
0.25
B;B;B;.;B;B;B;.;.;.
Vest4
0.63
MVP
0.043
MPC
0.59
ClinPred
0.17
T
GERP RS
3.9
Varity_R
0.044
gMVP
0.62

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: rs753086619; hg19: chr2-201334679; API