Variant 2-200467307-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001100423.2(SPATS2L):c.865C>T(p.Arg289Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,192 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATS2L	NM_001100423.2 linkuse as main transcript	c.865C>T	p.Arg289Cys	missense_variant	10/13	ENST00000409140.8	NP_001093893.1
LOC101927741	XR_007088047.1 linkuse as main transcript	n.569+8796G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATS2L	ENST00000409140.8 linkuse as main transcript	c.865C>T	p.Arg289Cys	missense_variant	10/13	2	NM_001100423.2	ENSP00000386730	P1	Q9NUQ6-1
	ENST00000655656.1 linkuse as main transcript	n.566+8796G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.865C>T (p.R289C) alteration is located in exon 10 (coding exon 8) of the SPATS2L gene. This alteration results from a C to T substitution at nucleotide position 865, causing the arginine (R) at amino acid position 289 to be replaced by a cysteine (C). 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

0.99

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.42

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

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.66

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.0067

MetaRNN

Pathogenic

0.91

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

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.7

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-7.5

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

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

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

Vest4

0.90

MutPred

0.80

Loss of MoRF binding (P = 0.0209);Loss of MoRF binding (P = 0.0209);Loss of MoRF binding (P = 0.0209);.;Loss of MoRF binding (P = 0.0209);.;Loss of MoRF binding (P = 0.0209);.;.;.;.;

MVP

0.40

MPC

1.1

ClinPred

1.0

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.96

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.

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