rs12599391

Variant names:

• chr16-69571446-T-C
• rs12599391
• NM_138713.4:c.127+2898T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.127+2898T>C		intron_variant	Intron 2 of 14	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.127+2898T>C		intron_variant	Intron 2 of 14	1	NM_138713.4	ENSP00000338806.3

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

African (AFR) AF: 0.226 AC: 9368 AN: 41452

American (AMR) AF: 0.350 AC: 5341 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3470

East Asian (EAS) AF: 0.118 AC: 610 AN: 5184

South Asian (SAS) AF: 0.313 AC: 1509 AN: 4828

European-Finnish (FIN) AF: 0.433 AC: 4554 AN: 10528

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28525 AN: 67970

Other (OTH) AF: 0.350 AC: 737 AN: 2108

Alfa AF: 0.381 Hom.: 1983

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
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12599391; hg19: chr16-69605349;