Variant 12-131719498-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004592.4(SFSWAP):c.565G>A(p.Val189Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,613,996 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 44 hom. )

Consequence

SFSWAP
NM_004592.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.287

Variant links:

Genes affected

SFSWAP (HGNC:10790): (splicing factor SWAP) This gene encodes a human homolog of Drosophila splicing regulatory protein. This gene autoregulates its expression by control of splicing of its first two introns. In addition, it also regulates the splicing of fibronectin and CD45 genes. Two transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

SFSWAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062130988).

BP6

Variant 12-131719498-G-A is Benign according to our data. Variant chr12-131719498-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643601.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 665 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFSWAP	NM_004592.4 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	4/18	ENST00000261674.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFSWAP	ENST00000261674.9 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	4/18	1	NM_004592.4	P4	Q12872-1

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

667

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00633

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00634

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00485

AC:

1220

AN:

251482

Hom.:

AF XY:

0.00540

AC XY:

734

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00960

Gnomad FIN exome

AF:

0.00785

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00560

AC:

8188

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

4247

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.00743

Gnomad4 NFE exome

AF:

0.00574

Gnomad4 OTH exome

AF:

0.00493

GnomAD4 genome

AF:

0.00437

AC:

665

AN:

152208

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.00633

Gnomad4 NFE

AF:

0.00634

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00502

Hom.:

Bravo

AF:

0.00351

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00497

AC:

603

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SFSWAP: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.1

DANN

Benign

0.81

DEOGEN2

Benign

0.094

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.58

N;N

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.031

Sift

Benign

0.59

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.012

B;.

Vest4

0.12

MVP

0.12

MPC

0.67

ClinPred

0.0058

GERP RS

-3.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.018

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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