chr16-68097829-G-A

Variant names:

• chr16-68097829-G-A
• rs9932251
• NM_173165.3:c.103+12045G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173165.3(NFATC3):​c.103+12045G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,956 control chromosomes in the GnomAD database, including 2,946 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 0.18 (2946 hom., cov: 31)
• Consequence: NFATC3 NM_173165.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 10 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]

ENSG00000261864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC3	NM_173165.3	MANE Select	c.103+12045G>A		intron	N/A	NP_775188.1
	NFATC3	NM_004555.4		c.103+12045G>A		intron	N/A	NP_004546.1
	NFATC3	NM_173163.3		c.103+12045G>A		intron	N/A	NP_775186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC3	ENST00000346183.8	TSL:1 MANE Select	c.103+12045G>A		intron	N/A	ENSP00000300659.5
	NFATC3	ENST00000329524.8	TSL:1	c.103+12045G>A		intron	N/A	ENSP00000331324.4
	NFATC3	ENST00000349223.9	TSL:1	c.103+12045G>A		intron	N/A	ENSP00000264008.6

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27931 AN: 151838 Hom.: 2937 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 27974 AN: 151956 Hom.: 2946 Cov.: 31 AF XY: 0.187 AC XY: 13893 AN XY: 74266

African (AFR) AF: 0.283 AC: 11714 AN: 41416

American (AMR) AF: 0.167 AC: 2542 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3468

East Asian (EAS) AF: 0.106 AC: 551 AN: 5182

South Asian (SAS) AF: 0.197 AC: 946 AN: 4808

European-Finnish (FIN) AF: 0.176 AC: 1854 AN: 10524

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9108 AN: 67982

Other (OTH) AF: 0.189 AC: 399 AN: 2114

Alfa AF: 0.152 Hom.: 1403

Bravo AF: 0.185

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.39
Mutation Taster		=100/0	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: rs9932251; hg19: chr16-68131732;