Genetic Variant NFAT5:c.*172A>G (chr16-69696523-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138713.4(NFAT5):c.*172A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,482 control chromosomes in the GnomAD database, including 33,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33617 hom., cov: 32)

Exomes 𝑓: 0.59 ( 77 hom. )

Consequence

NFAT5
NM_138713.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.534

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-69696523-A-G is Benign according to our data. Variant chr16-69696523-A-G is described in ClinVar as [Benign]. Clinvar id is 1227923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4 link	c.*172A>G		3_prime_UTR_variant	Exon 15 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.*172A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_138713.4	ENSP00000338806.3		O94916-5

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99848

AN:

151932

Hom.:

33563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.651

GnomAD4 exome

AF:

0.590

AC:

255

AN:

432

Hom.:

Cov.:

AF XY:

0.596

AC XY:

155

AN XY:

260

show subpopulations

Gnomad4 FIN exome

AF:

0.587

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.657

AC:

99972

AN:

152050

Hom.:

33617

Cov.:

AF XY:

0.658

AC XY:

48927

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.783

Gnomad4 AMR

AF:

0.653

Gnomad4 ASJ

AF:

0.572

Gnomad4 EAS

AF:

0.886

Gnomad4 SAS

AF:

0.688

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.581

Gnomad4 OTH

AF:

0.653

Alfa

AF:

0.605

Hom.:

27215

Bravo

AF:

0.672

Asia WGS

AF:

0.731

AC:

2533

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26506053) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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