Genetic Variant NM_138713.4:c.2691_2693delACA (chr16-69692513-TCAA-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_138713.4(NFAT5):c.2691_2693delACA(p.Gln898del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00136 in 1,614,070 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q897Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

NFAT5
NM_138713.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.82

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_138713.4

BP6

Variant 16-69692513-TCAA-T is Benign according to our data. Variant chr16-69692513-TCAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 456657.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4 link	c.2691_2693delACA	p.Gln898del	disruptive_inframe_deletion	Exon 13 of 15	ENST00000349945.7	NP_619727.2	O94916-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7 link	c.2691_2693delACA	p.Gln898del	disruptive_inframe_deletion	Exon 13 of 15	1	NM_138713.4	ENSP00000338806.3		O94916-5

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00136

AC:

342

AN:

250722

AF XY:

0.00152

show subpopulations

Gnomad AFR exome

AF:

0.000437

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00310

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00139

AC:

2025

AN:

1461848

Hom.:

AF XY:

0.00140

AC XY:

1019

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

114

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00264

AC:

141

AN:

53396

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00147

AC:

1633

AN:

1111992

Other (OTH)

AF:

0.00167

AC:

101

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

132

265

397

530

662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00114

AC:

174

AN:

152222

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41520

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

68002

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

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:

0.00199

Hom.:

Bravo

AF:

0.000929

EpiCase

AF:

0.00142

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NFAT5-related disorder

Benign:1

Apr 01, 2022

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). -

Immunodeficiency

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.8

Mutation Taster

=73/27

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