rs39999

Variant names:

• chr16-69619793-C-G
• rs39999
• NM_138713.4:c.128-6610C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138713.4(NFAT5):​c.128-6610C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,190 control chromosomes in the GnomAD database, including 60,617 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 0.89 (60617 hom., cov: 31)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.128-6610C>G		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.128-6610C>G		intron_variant	Intron 2 of 14	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135518 AN: 152072 Hom.: 60561 Cov.: 31

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.891 AC: 135632 AN: 152190 Hom.: 60617 Cov.: 31 AF XY: 0.893 AC XY: 66461 AN XY: 74410

African (AFR) AF: 0.959 AC: 39851 AN: 41540

American (AMR) AF: 0.873 AC: 13342 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.931 AC: 4816 AN: 5174

South Asian (SAS) AF: 0.870 AC: 4195 AN: 4820

European-Finnish (FIN) AF: 0.866 AC: 9172 AN: 10596

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58234 AN: 67988

Other (OTH) AF: 0.882 AC: 1860 AN: 2108

Alfa AF: 0.875 Hom.: 7261

Bravo AF: 0.893

Asia WGS AF: 0.897 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.41
PhyloP100		-0.095
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: rs39999; hg19: chr16-69653696;