rs12598

Positions:

• chr16-68191612-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173165.3(NFATC3):​c.2943G>A​(p.Thr981Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,614,022 control chromosomes in the GnomAD database, including 6,166 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 0.057 (330 hom., cov: 31)
  • Exomes 𝑓: 0.084 (5836 hom.)
• Consequence: NFATC3 NM_173165.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

NFATC3 (HGNC:7777): (nuclear factor of activated T cells 3) The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Nov 2010]

NFATC3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.385 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC3	NM_173165.3	c.2943G>A	p.Thr981Thr	synonymous_variant	9/10	ENST00000346183.8	NP_775188.1
NFATC3	NM_004555.4	c.2943G>A	p.Thr981Thr	synonymous_variant	9/11		NP_004546.1
NFATC3	NM_173163.3	c.2943G>A	p.Thr981Thr	synonymous_variant	9/11		NP_775186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC3	ENST00000346183.8	c.2943G>A	p.Thr981Thr	synonymous_variant	9/10	1	NM_173165.3	ENSP00000300659.5

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8643 AN: 152026 Hom.: 330 Cov.: 31

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0633 AC: 15909 AN: 251466 Hom.: 722 AF XY: 0.0662 AC XY: 8998 AN XY: 135906

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.000652

Gnomad SAS exome AF: 0.0778

Gnomad FIN exome AF: 0.0818

Gnomad NFE exome AF: 0.0896

Gnomad OTH exome AF: 0.0600

GnomAD4 exome AF: 0.0844 AC: 123428 AN: 1461878 Hom.: 5836 Cov.: 32 AF XY: 0.0839 AC XY: 61041 AN XY: 727242

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0206

Gnomad4 ASJ exome AF: 0.0254

Gnomad4 EAS exome AF: 0.000705

Gnomad4 SAS exome AF: 0.0784

Gnomad4 FIN exome AF: 0.0804

Gnomad4 NFE exome AF: 0.0954

Gnomad4 OTH exome AF: 0.0674

GnomAD4 genome AF: 0.0568 AC: 8642 AN: 152144 Hom.: 330 Cov.: 31 AF XY: 0.0551 AC XY: 4096 AN XY: 74376

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0260

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0794 Hom.: 971

Bravo AF: 0.0506

Asia WGS AF: 0.0250 AC: 87 AN: 3478

EpiCase AF: 0.0829

EpiControl AF: 0.0803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs12598; hg19: chr16-68225515;