16-69694071-C-G

Variant names:

• chr16-69694071-C-G
• rs1202614548
• NM_138713.4:c.4246C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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. 16/21 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
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1794172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138713.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	NM_138713.4	MANE Select	c.4246C>G	p.Leu1416Val	missense	Exon 13 of 15	NP_619727.2
	NFAT5	NM_001113178.3		c.4243C>G	p.Leu1415Val	missense	Exon 13 of 15	NP_001106649.1
	NFAT5	NM_006599.4		c.4192C>G	p.Leu1398Val	missense	Exon 12 of 14	NP_006590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	ENST00000349945.7	TSL:1 MANE Select	c.4246C>G	p.Leu1416Val	missense	Exon 13 of 15	ENSP00000338806.3
	NFAT5	ENST00000567239.5	TSL:1	c.4243C>G	p.Leu1415Val	missense	Exon 13 of 15	ENSP00000457593.1
	NFAT5	ENST00000354436.6	TSL:1	c.4192C>G	p.Leu1398Val	missense	Exon 12 of 14	ENSP00000346420.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.085
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.11
Sift	Benign	0.12	T
Sift4G	Benign	0.43	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

Other links and lift over

dbSNP: rs1202614548; hg19: chr16-69727974;