16-69703943-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138713.4(NFAT5):c.*7592G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,454 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.092 (889 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: NFAT5 NM_138713.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAT5	NM_138713.4	c.*7592G>C		3_prime_UTR_variant	15/15	ENST00000349945.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAT5	ENST00000349945.7	c.*7592G>C		3_prime_UTR_variant	15/15	1	NM_138713.4	A2
	ENST00000561622.1	n.879G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14001 AN: 151948 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.144 AC: 56 AN: 388 Hom.: 3 Cov.: 0 AF XY: 0.144 AC XY: 36 AN XY: 250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0921 AC: 14004 AN: 152066 Hom.: 889 Cov.: 32 AF XY: 0.0944 AC XY: 7016 AN XY: 74304

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.102 Hom.: 122

Bravo AF: 0.0841

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	6.2
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2965757; hg19: chr16-69737846;