rs12599391

Positions:

• chr16-69571446-T-C

Variant summary

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

The NM_138713.4(NFAT5):​c.127+2898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,998 control chromosomes in the GnomAD database, including 9,784 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 0.35 (9784 hom., cov: 31)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.127+2898T>C		intron_variant		ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.127+2898T>C		intron_variant		1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52583 AN: 151880 Hom.: 9796 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.346 AC: 52576 AN: 151998 Hom.: 9784 Cov.: 31 AF XY: 0.345 AC XY: 25634 AN XY: 74274

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.350

Alfa AF: 0.385 Hom.: 1955

Bravo AF: 0.332

Asia WGS AF: 0.270 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.3
DANN	Benign	0.68

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: rs12599391; hg19: chr16-69605349;