Variant chr2-200419320-G-T 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.269G>T(p.Arg90Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SPATS2L
NM_001100423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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.269G>T	p.Arg90Met	missense_variant	6/13	ENST00000409140.8	NP_001093893.1
LOC101927741	XR_007088047.1 linkuse as main transcript	n.911-7812C>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.269G>T	p.Arg90Met	missense_variant	6/13	2	NM_001100423.2	ENSP00000386730	P1	Q9NUQ6-1
	ENST00000655656.1 linkuse as main transcript	n.814+10103C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Mar 12, 2024

The c.269G>T (p.R90M) alteration is located in exon 6 (coding exon 4) of the SPATS2L gene. This alteration results from a G to T substitution at nucleotide position 269, causing the arginine (R) at amino acid position 90 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0093

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

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

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

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.52

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

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.2

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

MutationTaster

Benign

0.70

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

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.39

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

REVEL

Uncertain

0.32

Sift

Uncertain

0.010

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

Sift4G

Uncertain

0.049

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

Polyphen

0.99, 0.99

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

Vest4

0.43, 0.40, 0.42, 0.41, 0.41

MutPred

0.51

Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);.;Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);.;.;Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);.;

MVP

0.12

MPC

0.96

ClinPred

0.76

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.48

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