rs1202614548

chr16-69694071-C-Gchr16-69694071-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_138713.4(NFAT5):c.4246C>G(p.Leu1416Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1416F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFAT5 NM_138713.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, NFAT5
• BP4: Computational evidence support a benign effect (MetaRNN=0.1794172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAT5	NM_138713.4	c.4246C>G	p.Leu1416Val	missense_variant	13/15	ENST00000349945.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAT5	ENST00000349945.7	c.4246C>G	p.Leu1416Val	missense_variant	13/15	1	NM_138713.4	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	20
Dann	Uncertain	0.99
Eigen	Benign	0.085
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D;D;D;.;.
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	0.52	N;N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.13	N;N;N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.12	T;T;T;.;T;T
Sift4G	Benign	0.43	T;T;T;T;T;T
Polyphen		0.31	.;B;.;.;.;.
Vest4		0.29
MutPred		0.13		.;Loss of glycosylation at P1397 (P = 0.095);.;.;.;.;
MVP		0.40
ClinPred		0.31	T
GERP RS		4.9
Varity_R		0.090

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1202614548; hg19: chr16-69727974;