chr2-200440744-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001100423.2(SPATS2L):​c.748G>A​(p.Val250Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,620 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: 0.000012 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39907706).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPATS2LNM_001100423.2 linkuse as main transcriptc.748G>A p.Val250Met missense_variant 8/13 ENST00000409140.8
LOC101927741XR_007088047.1 linkuse as main transcriptn.662+8632C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPATS2LENST00000409140.8 linkuse as main transcriptc.748G>A p.Val250Met missense_variant 8/132 NM_001100423.2 P1Q9NUQ6-1
ENST00000655656.1 linkuse as main transcriptn.567-9207C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
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:
0.0000281
AC:
7
AN:
248776
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134938
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000223
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461314
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
726914
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000414
AC:
5

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 GeneticsAug 30, 2021The c.748G>A (p.V250M) alteration is located in exon 8 (coding exon 6) of the SPATS2L gene. This alteration results from a G to A substitution at nucleotide position 748, causing the valine (V) at amino acid position 250 to be replaced by a methionine (M). 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
0.50
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.093
T;T;T;T;T;.;T;T;T;.;.;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
.;.;.;D;.;D;D;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.40
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.1
M;M;M;.;M;.;.;M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.5
N;N;N;N;N;N;N;N;N;.;N;N
REVEL
Uncertain
0.29
Sift
Uncertain
0.0070
D;D;D;D;D;D;D;D;D;.;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;D;D;D;D;D;.;D
Polyphen
1.0
D;D;D;.;D;D;.;D;.;.;.;.
Vest4
0.55
MutPred
0.61
Gain of catalytic residue at V246 (P = 0.0201);Gain of catalytic residue at V246 (P = 0.0201);Gain of catalytic residue at V246 (P = 0.0201);.;Gain of catalytic residue at V246 (P = 0.0201);.;.;Gain of catalytic residue at V246 (P = 0.0201);.;.;.;.;
MVP
0.13
MPC
0.85
ClinPred
0.65
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.19
gMVP
0.95

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: rs562876187; hg19: chr2-201305467; API