Genetic Variant SPATS2:p.Val22Ile (chr12-49484628-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_023071.4(SPATS2):c.64G>A(p.Val22Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,613,880 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 56 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 50 hom. )

Consequence

SPATS2
NM_023071.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.75

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003194213).

BP6

Variant 12-49484628-G-A is Benign according to our data. Variant chr12-49484628-G-A is described in ClinVar as [Benign]. Clinvar id is 787394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATS2	NM_023071.4 link	c.64G>A	p.Val22Ile	missense_variant	Exon 4 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.64G>A	p.Val22Ile	missense_variant	Exon 4 of 14	2	NM_023071.4	ENSP00000447947.2		Q86XZ4

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2263

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00424

AC:

1067

AN:

251374

Hom.:

AF XY:

0.00311

AC XY:

422

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0558

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00168

AC:

2461

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1069

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0532

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00574

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0149

AC:

2268

AN:

152172

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1071

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0515

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.0169

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0499

AC:

220

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00518

AC:

629

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

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

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

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

MetaRNN

Benign

0.0032

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

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.5

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

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.54

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.071

T;T;D;T;D;T;T;T;T;D

Sift4G

Benign

0.091

T;T;D;T;D;T;T;T;T;D

Polyphen

1.0

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

Vest4

0.37, 0.50

MVP

0.38

MPC

0.67

ClinPred

0.045

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.083

gMVP

0.24

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