chr16-68191612-G-A

Variant names:

• chr16-68191612-G-A
• rs12598
• NM_173165.3:c.2943G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173165.3. 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
	NFATC3	NM_173165.3	MANE Select	c.2943G>A	p.Thr981Thr	synonymous	Exon 9 of 10	NP_775188.1	B5B2S1
	NFATC3	NM_004555.4		c.2943G>A	p.Thr981Thr	synonymous	Exon 9 of 11	NP_004546.1	B5B2S0
	NFATC3	NM_173163.3		c.2943G>A	p.Thr981Thr	synonymous	Exon 9 of 11	NP_775186.1	Q12968-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC3	ENST00000346183.8	TSL:1 MANE Select	c.2943G>A	p.Thr981Thr	synonymous	Exon 9 of 10	ENSP00000300659.5	Q12968-1
	NFATC3	ENST00000329524.8	TSL:1	c.2943G>A	p.Thr981Thr	synonymous	Exon 9 of 11	ENSP00000331324.4	Q12968-2
	NFATC3	ENST00000349223.9	TSL:1	c.2943G>A	p.Thr981Thr	synonymous	Exon 9 of 11	ENSP00000264008.6	Q12968-3

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

GnomAD2 exomes AF: 0.0633 AC: 15909 AN: 251466 AF XY: 0.0662

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 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

African (AFR) AF: 0.0122 AC: 407 AN: 33480

American (AMR) AF: 0.0206 AC: 920 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 663 AN: 26136

East Asian (EAS) AF: 0.000705 AC: 28 AN: 39700

South Asian (SAS) AF: 0.0784 AC: 6759 AN: 86258

European-Finnish (FIN) AF: 0.0804 AC: 4294 AN: 53420

Middle Eastern (MID) AF: 0.0338 AC: 195 AN: 5768

European-Non Finnish (NFE) AF: 0.0954 AC: 106089 AN: 1111996

Other (OTH) AF: 0.0674 AC: 4073 AN: 60396

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

African (AFR) AF: 0.0155 AC: 644 AN: 41522

American (AMR) AF: 0.0267 AC: 408 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 90 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5172

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4820

European-Finnish (FIN) AF: 0.0821 AC: 869 AN: 10582

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6188 AN: 67992

Other (OTH) AF: 0.0341 AC: 72 AN: 2112

Alfa AF: 0.0782 Hom.: 1267

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.72
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs12598; hg19: chr16-68225515;