2-200469935-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001100423.2(SPATS2L):ā€‹c.979T>Cā€‹(p.Tyr327His) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,611,150 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.754

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPATS2LNM_001100423.2 linkuse as main transcriptc.979T>C p.Tyr327His missense_variant 11/13 ENST00000409140.8 NP_001093893.1
LOC101927741XR_007088047.1 linkuse as main transcriptn.569+6168A>G 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.979T>C p.Tyr327His missense_variant 11/132 NM_001100423.2 ENSP00000386730 P1Q9NUQ6-1
ENST00000655656.1 linkuse as main transcriptn.566+6168A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000123
AC:
3
AN:
244656
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132474
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000880
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:
1458988
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
725366
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000450
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000828
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsApr 23, 2024The c.979T>C (p.Y327H) alteration is located in exon 11 (coding exon 9) of the SPATS2L gene. This alteration results from a T to C substitution at nucleotide position 979, causing the tyrosine (Y) at amino acid position 327 to be replaced by a histidine (H). 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
1.0
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;T;T;T;T;.;T;T;.;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
.;.;.;D;.;D;D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.75
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.3
M;M;M;.;M;.;M;.;.;.
MutationTaster
Benign
0.99
D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.3
D;D;D;D;D;D;D;D;.;D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0060
D;D;D;D;D;D;D;D;.;D
Sift4G
Uncertain
0.015
D;D;D;D;D;D;D;D;D;.
Polyphen
1.0
D;D;D;.;D;D;D;.;.;.
Vest4
0.84
MutPred
0.72
Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);.;Gain of disorder (P = 0.0209);.;Gain of disorder (P = 0.0209);.;.;.;
MVP
0.17
MPC
1.1
ClinPred
0.89
D
GERP RS
5.0
Varity_R
0.37
gMVP
0.76

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: rs751090740; hg19: chr2-201334658; API