16-69696523-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.534

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
NFAT5	NM_138713.4	c.*172A>G		3_prime_UTR_variant	15/15	ENST00000349945.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAT5	ENST00000349945.7	c.*172A>G		3_prime_UTR_variant	15/15	1	NM_138713.4	A2

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99848 AN: 151932 Hom.: 33563 Cov.: 32

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.: 77 Cov.: 0 AF XY: 0.596 AC XY: 155 AN XY: 260

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.: 32 AF XY: 0.658 AC XY: 48927 AN XY: 74326

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

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	11
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

Other links and lift over

dbSNP: rs1437134; hg19: chr16-69730426;