chr18-79400399-G-A

Variant names:

• chr18-79400399-G-A
• rs1249819200
• ENST00000329101.8:c.8G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172387.3(NFATC1):​c.8G>A​(p.Gly3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFATC1 NM_172387.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.749
• Publications: 0 publications found

Genes affected

NFATC1 (HGNC:7775): (nuclear factor of activated T cells 1) The product of this gene is a component of the nuclear factor 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. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [provided by RefSeq, Jul 2013]

NFATC1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

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=0.23716128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172387.3. 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
	NFATC1	NM_001278669.2	MANE Select	c.127+4048G>A		intron	N/A	NP_001265598.1	O95644-1
	NFATC1	NM_172387.3		c.8G>A	p.Gly3Glu	missense	Exon 1 of 10	NP_765975.1	O95644-6
	NFATC1	NM_172389.3		c.8G>A	p.Gly3Glu	missense	Exon 1 of 10	NP_765977.1	O95644-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000329101.8	TSL:1	c.8G>A	p.Gly3Glu	missense	Exon 1 of 10	ENSP00000327850.3	O95644-6
	NFATC1	ENST00000318065.9	TSL:1	c.8G>A	p.Gly3Glu	missense	Exon 1 of 10	ENSP00000316553.5	O95644-5
	NFATC1	ENST00000592223.5	TSL:1	c.8G>A	p.Gly3Glu	missense	Exon 1 of 8	ENSP00000467181.1	O95644-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1338466 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 660438

African (AFR) AF: 0.00 AC: 0 AN: 26722

American (AMR) AF: 0.00 AC: 0 AN: 27514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23162

East Asian (EAS) AF: 0.00 AC: 0 AN: 28828

South Asian (SAS) AF: 0.00 AC: 0 AN: 73836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051332

Other (OTH) AF: 0.00 AC: 0 AN: 54852

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.0086
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.75
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.27
MutPred		0.29		Gain of solvent accessibility (P = 0.0281)
MVP		0.082
MPC		0.93
ClinPred		0.99	D
GERP RS		3.4
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=95/5	polymorphism

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: rs1249819200; hg19: chr18-77160399;