Genetic Variant SPATS2L:p.Val10Ile (chr2-200389272-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100423.2(SPATS2L):c.28G>A(p.Val10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,431,592 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.421

Publications

0 publications found

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]

SPATS2L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025177151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATS2L	NM_001100423.2 link	c.28G>A	p.Val10Ile	missense_variant	Exon 3 of 13	ENST00000409140.8	NP_001093893.1	Q9NUQ6-1A0A024R3V0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATS2L	ENST00000409140.8 link	c.28G>A	p.Val10Ile	missense_variant	Exon 3 of 13	2	NM_001100423.2	ENSP00000386730.3		Q9NUQ6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1431592

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

709208

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33020

American (AMR)

AF:

0.00

AC:

AN:

41034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25572

East Asian (EAS)

AF:

0.00

AC:

AN:

38892

South Asian (SAS)

AF:

0.0000246

AC:

AN:

81448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1094742

Other (OTH)

AF:

0.00

AC:

AN:

59312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 14, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.28G>A (p.V10I) alteration is located in exon 3 (coding exon 1) of the SPATS2L gene. This alteration results from a G to A substitution at nucleotide position 28, causing the valine (V) at amino acid position 10 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

0.085

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0035

T;T;T;T;T;T;T;.;T;.;T;T;T;T;.;.;.;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.72

T;.;.;.;T;T;.;T;T;.;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.025

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.9

.;N;N;N;.;.;N;N;.;.;.;.;N;.;.;.;.;.

PhyloP100

0.42

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.26

N;N;N;N;N;N;N;N;N;N;N;N;N;N;.;N;N;N

REVEL

Benign

0.025

Sift

Benign

1.0

T;T;T;T;T;.;T;T;T;.;T;T;T;T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;.;T;T

Polyphen

0.0, 0.0010

.;B;B;B;.;.;B;B;.;.;.;.;B;.;.;.;.;.

Vest4

0.13, 0.12, 0.12, 0.11

MutPred

0.28

Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);.;.;Loss of methylation at K11 (P = 0.0628);Loss of methylation at K11 (P = 0.0628);

MVP

0.043

MPC

0.22

ClinPred

0.075

GERP RS

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.11

Mutation Taster

=89/11

polymorphism

(source)

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

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2-200389272-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over