18-79410424-C-G

Variant names:

• chr18-79410424-C-G
• rs763800698
• NM_001278669.2:c.149C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001278669.2(NFATC1):​c.149C>G​(p.Ser50Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NFATC1 NM_001278669.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27731836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC1	NM_001278669.2	c.149C>G	p.Ser50Cys	missense_variant	Exon 2 of 10	ENST00000427363.7	NP_001265598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC1	ENST00000427363.7	c.149C>G	p.Ser50Cys	missense_variant	Exon 2 of 10	1	NM_001278669.2	ENSP00000389377.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246448 Hom.: 0 AF XY: 0.00000749 AC XY: 1 AN XY: 133484

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458710 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	.;.;T;.;T;.;.;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.055
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.28	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;M;.;M;M;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.89	N;.;.;N;N;.;.;N;.
REVEL	Benign	0.20
Sift	Benign	0.033	D;.;.;D;D;.;.;T;.
Sift4G	Benign	0.10	T;T;T;T;T;T;T;T;T
Polyphen		0.98	.;.;.;.;D;.;.;.;.
Vest4		0.43
MutPred		0.25		Loss of glycosylation at S50 (P = 0.0135);Loss of glycosylation at S50 (P = 0.0135);Loss of glycosylation at S50 (P = 0.0135);Loss of glycosylation at S50 (P = 0.0135);Loss of glycosylation at S50 (P = 0.0135);.;.;.;.;
MVP		0.40
MPC		0.75
ClinPred		0.70	D
GERP RS		4.4
Varity_R		0.074
gMVP		0.18

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: rs763800698; hg19: chr18-77170424;