Genetic Variant SPATS2L:p.Gln178Lys (chr2-200439208-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001100423.2(SPATS2L):c.532C>A(p.Gln178Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,344 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

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:

ENSG00000287299 (HGNC:):

ENSG00000287299 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31083214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATS2L	NM_001100423.2 link	c.532C>A	p.Gln178Lys	missense_variant	Exon 7 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.532C>A	p.Gln178Lys	missense_variant	Exon 7 of 13	2	NM_001100423.2	ENSP00000386730.3		Q9NUQ6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461344

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111626

Other (OTH)

AF:

0.0000166

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000279

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 11, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.532C>A (p.Q178K) alteration is located in exon 7 (coding exon 5) of the SPATS2L gene. This alteration results from a C to A substitution at nucleotide position 532, causing the glutamine (Q) at amino acid position 178 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.072

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

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.31

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

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.2

L;L;L;.;L;.;L;.;.

PhyloP100

4.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.89

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

REVEL

Benign

0.18

Sift

Uncertain

0.016

D;D;D;D;D;D;D;.;D

Sift4G

Benign

0.48

T;T;T;T;T;D;T;T;.

Polyphen

0.099

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

Vest4

0.32

MutPred

0.58

Gain of ubiquitination at Q178 (P = 0.0037);Gain of ubiquitination at Q178 (P = 0.0037);Gain of ubiquitination at Q178 (P = 0.0037);.;Gain of ubiquitination at Q178 (P = 0.0037);Gain of ubiquitination at Q178 (P = 0.0037);Gain of ubiquitination at Q178 (P = 0.0037);.;.;

MVP

0.068

MPC

0.54

ClinPred

0.59

GERP RS

5.3

Varity_R

0.22

gMVP

0.68

Mutation Taster

=76/24

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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2-200439208-C-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