2-200412340-C-A

Variant names:

Variant summary

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

The NM_001100423.2(SPATS2L):c.69C>A(p.Asn23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,598,278 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N23Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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:

Genome browser will be placed here

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=0.39001632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATS2L	NM_001100423.2 link	c.69C>A	p.Asn23Lys	missense_variant	Exon 4 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.69C>A	p.Asn23Lys	missense_variant	Exon 4 of 13	2	NM_001100423.2	ENSP00000386730.3		Q9NUQ6-1

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

148994

Hom.:

Cov.:

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:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

237976

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.0000682

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1449284

Hom.:

Cov.:

AF XY:

0.00000833

AC XY:

AN XY:

720330

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33060

American (AMR)

AF:

0.00

AC:

AN:

43730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25898

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.0000359

AC:

AN:

83674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000724

AC:

AN:

1104882

Other (OTH)

AF:

0.0000667

AC:

AN:

59946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000671

AC:

AN:

148994

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40236

American (AMR)

AF:

0.00

AC:

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.000211

AC:

AN:

4734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67538

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.69C>A (p.N23K) alteration is located in exon 4 (coding exon 2) of the SPATS2L gene. This alteration results from a C to A substitution at nucleotide position 69, causing the asparagine (N) at amino acid position 23 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

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

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.027

MetaRNN

Benign

0.32

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

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.1

.;M;M;M;.;.;M;M;.;.;.;M;.;.;.;.;.;.

PhyloP100

1.9

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.7

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

REVEL

Benign

0.13

Sift

Uncertain

0.0030

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0, 1.0

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

Vest4

0.76, 0.73, 0.77, 0.76

MutPred

0.33

Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);.;.;Gain of methylation at N23 (P = 0.0172);Gain of methylation at N23 (P = 0.0172);.;

MVP

0.13

MPC

1.0

ClinPred

0.92

GERP RS

1.8

Varity_R

0.54

gMVP

0.58

Mutation Taster

=45/55

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-200412340-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over