Genetic Variant SPATS2:p.Met263Thr (chr12-49500154-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_023071.4(SPATS2):c.788T>C(p.Met263Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

SPATS2
NM_023071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

Variant links:

Genes affected

SPATS2 (HGNC:18650): (spermatogenesis associated serine rich 2) Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SPATS2 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 rank	MANE	Protein	UniProt
SPATS2	NM_023071.4 link	c.788T>C	p.Met263Thr	missense_variant	Exon 9 of 14	ENST00000552918.6	NP_075559.2	Q86XZ4A0A024R101

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATS2	ENST00000552918.6 link	c.788T>C	p.Met263Thr	missense_variant	Exon 9 of 14	2	NM_023071.4	ENSP00000447947.2		Q86XZ4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249228

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459506

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.000165

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.788T>C (p.M263T) alteration is located in exon 9 (coding exon 7) of the SPATS2 gene. This alteration results from a T to C substitution at nucleotide position 788, causing the methionine (M) at amino acid position 263 to be replaced by a threonine (T). 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

0.84

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;.;D

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.4

M;M;M

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.024

D;D;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.65

MutPred

0.61

Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);

MVP

0.24

MPC

0.80

ClinPred

0.89

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.42

gMVP

0.64

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