Variant rs61730073 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138713.4(NFAT5):c.3351T>C(p.Ile1117Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00811 in 1,614,074 control chromosomes in the GnomAD database, including 952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 511 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 441 hom. )

Consequence

NFAT5
NM_138713.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.796

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:

NFAT5 (HGNC:):

NFAT5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 16-69693176-T-C is Benign according to our data. Variant chr16-69693176-T-C is described in ClinVar as [Benign]. Clinvar id is 456658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.796 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4 linkuse as main transcript	c.3351T>C	p.Ile1117Ile	synonymous_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 linkuse as main transcript	c.3351T>C	p.Ile1117Ile	synonymous_variant	13/15	1	NM_138713.4	ENSP00000338806.3		O94916-5

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6738

AN:

152076

Hom.:

513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0326

GnomAD3 exomes

AF:

0.0112

AC:

2804

AN:

251340

Hom.:

189

AF XY:

0.00832

AC XY:

1131

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00434

AC:

6349

AN:

1461880

Hom.:

441

Cov.:

AF XY:

0.00379

AC XY:

2758

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.00639

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00929

GnomAD4 genome

AF:

0.0443

AC:

6738

AN:

152194

Hom.:

511

Cov.:

AF XY:

0.0434

AC XY:

3229

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0235

Hom.:

100

Bravo

AF:

0.0494

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

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

Jul 11, 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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.0

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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