Variant 2-200477638-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001100423.2(SPATS2L):c.1284T>G(p.Asn428Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,541,244 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 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.638

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATS2L	NM_001100423.2 linkuse as main transcript	c.1284T>G	p.Asn428Lys	missense_variant, splice_region_variant	13/13	ENST00000409140.8	NP_001093893.1
LOC101927741	XR_007088047.1 linkuse as main transcript	n.336A>C		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATS2L	ENST00000409140.8 linkuse as main transcript	c.1284T>G	p.Asn428Lys	missense_variant, splice_region_variant	13/13	2	NM_001100423.2	ENSP00000386730	P1	Q9NUQ6-1
	ENST00000655656.1 linkuse as main transcript	n.333A>C		non_coding_transcript_exon_variant	1/5

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.0000506

AC:

AN:

158090

Hom.:

AF XY:

0.0000357

AC XY:

AN XY:

83932

show subpopulations

Gnomad AFR exome

AF:

0.000783

Gnomad AMR exome

AF:

0.0000434

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:

0.0000324

AC:

AN:

1389326

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

684336

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.0000299

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:

9.31e-7

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

AF:

0.000408

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.00138

Gnomad4 AMR

AF:

0.000328

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

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.000530

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000514

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.1284T>G (p.N428K) alteration is located in exon 13 (coding exon 11) of the SPATS2L gene. This alteration results from a T to G substitution at nucleotide position 1284, causing the asparagine (N) at amino acid position 428 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

0.65

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

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

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.010

MetaRNN

Benign

0.033

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

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

MutationTaster

Benign

0.97

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.2

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

REVEL

Benign

0.089

Sift

Uncertain

0.016

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

Sift4G

Benign

0.83

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

Polyphen

0.70

P;P;P;.;P;P;P;.;.

Vest4

0.31

MutPred

0.18

Gain of methylation at N428 (P = 0.0098);Gain of methylation at N428 (P = 0.0098);Gain of methylation at N428 (P = 0.0098);.;Gain of methylation at N428 (P = 0.0098);.;Gain of methylation at N428 (P = 0.0098);.;.;

MVP

0.068

MPC

0.44

ClinPred

0.072

GERP RS

3.0

Varity_R

0.072

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: 1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over