Genetic Variant NFAT5:p.Glu842Glu (chr16-69692351-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_138713.4(NFAT5):c.2526G>A(p.Glu842Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 1,614,198 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 16 hom., cov: 32)

Exomes 𝑓: 0.010 ( 99 hom. )

Consequence

NFAT5
NM_138713.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.740

Publications

7 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 16-69692351-G-A is Benign according to our data. Variant chr16-69692351-G-A is described in ClinVar as Benign. ClinVar VariationId is 456656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.74 with no splicing effect.

BS2

High AC in GnomAd4 at 1203 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138713.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NFAT5	NM_138713.4	MANE Select	c.2526G>A	p.Glu842Glu	synonymous	Exon 13 of 15	NP_619727.2
NFAT5	NM_001113178.3		c.2523G>A	p.Glu841Glu	synonymous	Exon 13 of 15	NP_001106649.1
NFAT5	NM_006599.4		c.2472G>A	p.Glu824Glu	synonymous	Exon 12 of 14	NP_006590.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NFAT5	ENST00000349945.7	TSL:1 MANE Select	c.2526G>A	p.Glu842Glu	synonymous	Exon 13 of 15	ENSP00000338806.3
NFAT5	ENST00000567239.5	TSL:1	c.2523G>A	p.Glu841Glu	synonymous	Exon 13 of 15	ENSP00000457593.1
NFAT5	ENST00000354436.6	TSL:1	c.2472G>A	p.Glu824Glu	synonymous	Exon 12 of 14	ENSP00000346420.2

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1202

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00594

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00859

AC:

2160

AN:

251352

AF XY:

0.00876

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00590

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00799

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.00896

GnomAD4 exome

AF:

0.0100

AC:

14650

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00996

AC XY:

7245

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33480

American (AMR)

AF:

0.00619

AC:

277

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

469

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00457

AC:

394

AN:

86258

European-Finnish (FIN)

AF:

0.00702

AC:

375

AN:

53420

Middle Eastern (MID)

AF:

0.00954

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0112

AC:

12482

AN:

1112010

Other (OTH)

AF:

0.00929

AC:

561

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

934

1868

2801

3735

4669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.00790

AC:

1203

AN:

152306

Hom.:

Cov.:

AF XY:

0.00761

AC XY:

567

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41574

American (AMR)

AF:

0.0120

AC:

183

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00594

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

741

AN:

68028

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

120

181

241

301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00957

Hom.:

Bravo

AF:

0.00801

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NFAT5: BP4, BP7, BS1, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

NFAT5-related disorder

Benign:1

Jul 03, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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).

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.1

(source)

DANN

Benign

0.66

PhyloP100

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=78/22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over