rs145602190

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_138713.4(NFAT5):c.3752A>G(p.Gln1251Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00506 in 1,614,176 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q1251Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 29 hom. )

Consequence

NFAT5
NM_138713.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.99

Publications

10 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011267871).

BP6

Variant 16-69693577-A-G is Benign according to our data. Variant chr16-69693577-A-G is described in ClinVar as Benign. ClinVar VariationId is 456659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4 link	c.3752A>G	p.Gln1251Arg	missense_variant	Exon 13 of 15	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7 link	c.3752A>G	p.Gln1251Arg	missense_variant	Exon 13 of 15	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

543

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00567

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00354

AC:

889

AN:

251318

AF XY:

0.00357

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00612

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00521

AC:

7622

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3704

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000806

AC:

AN:

33480

American (AMR)

AF:

0.00259

AC:

116

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000406

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00352

AC:

188

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00631

AC:

7018

AN:

1112010

Other (OTH)

AF:

0.00382

AC:

231

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

548

1095

1643

2190

2738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00357

AC:

543

AN:

152286

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

253

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41566

American (AMR)

AF:

0.00406

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00567

AC:

386

AN:

68022

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00487

Hom.:

Bravo

AF:

0.00322

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00346

AC:

420

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00498

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

NFAT5-related disorder

Benign:1

Feb 24, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

not provided

Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NFAT5: BP4, BS1, BS2

Immunodeficiency

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0

.;D;.;.;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

D;D;D;D;.;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.0

.;M;.;.;.;.

PhyloP100

7.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.94

N;N;N;.;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;D;D;.;D;D

Sift4G

Uncertain

0.056

T;T;T;T;T;T

Vest4

0.75

ClinPred

0.029

GERP RS

4.8

Varity_R

0.43

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over