chr16-69692980-A-G

Variant names:

• chr16-69692980-A-G
• rs1555534626
• NM_138713.4:c.3155A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138713.4(NFAT5):​c.3155A>G​(p.Gln1052Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFAT5 NM_138713.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	NM_138713.4	MANE Select	c.3155A>G	p.Gln1052Arg	missense	Exon 13 of 15	NP_619727.2	O94916-5
	NFAT5	NM_001113178.3		c.3152A>G	p.Gln1051Arg	missense	Exon 13 of 15	NP_001106649.1	O94916-4
	NFAT5	NM_006599.4		c.3101A>G	p.Gln1034Arg	missense	Exon 12 of 14	NP_006590.1	O94916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	ENST00000349945.7	TSL:1 MANE Select	c.3155A>G	p.Gln1052Arg	missense	Exon 13 of 15	ENSP00000338806.3	O94916-5
	NFAT5	ENST00000567239.5	TSL:1	c.3152A>G	p.Gln1051Arg	missense	Exon 13 of 15	ENSP00000457593.1	O94916-4
	NFAT5	ENST00000354436.6	TSL:1	c.3101A>G	p.Gln1034Arg	missense	Exon 12 of 14	ENSP00000346420.2	O94916-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Immunodeficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.031	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.24		Gain of MoRF binding (P = 0.0197)
MVP		0.65
ClinPred		0.90	D
GERP RS		6.0
Varity_R		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555534626; hg19: chr16-69726883;