Variant rs56368098 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_138713.4(NFAT5):c.1969T>G(p.Ser657Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,614,096 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 12 hom. )

Consequence

NFAT5
NM_138713.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

NFAT5 (HGNC:7774): (nuclear factor of activated T cells 5) The product of this gene is a member of the nuclear factors of activated T cells family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

NFAT5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050411224).

BP6

Variant 16-69691794-T-G is Benign according to our data. Variant chr16-69691794-T-G is described in ClinVar as [Benign]. Clinvar id is 526786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-69691794-T-G is described in Lovd as [Likely_benign]. Variant chr16-69691794-T-G is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4 link	c.1969T>G	p.Ser657Ala	missense_variant	13/15	ENST00000349945.7	NP_619727.2	O94916-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7 link	c.1969T>G	p.Ser657Ala	missense_variant	13/15	1	NM_138713.4	ENSP00000338806.3		O94916-5

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00228

AC:

572

AN:

251330

Hom.:

AF XY:

0.00238

AC XY:

323

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00324

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00259

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00238

AC:

3483

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

1763

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00861

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00238

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00162

AC:

246

AN:

152232

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00192

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00226

AC:

274

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00290

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

NFAT5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Immunodeficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

.;T;.;.;.;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T;T;T;.;.

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0050

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

.;L;.;.;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.78

N;N;N;.;N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0040

D;D;D;.;D;D

Sift4G

Benign

0.22

T;T;T;T;T;T

Polyphen

0.18

.;B;.;.;.;.

Vest4

0.29

MVP

0.60

ClinPred

0.034

GERP RS

6.1

Varity_R

0.11

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