18-79396261-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278669.2(NFATC1):c.37C>T(p.Pro13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,337,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P13L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

NFATC1
NM_001278669.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.134

Publications

0 publications found

Variant links:

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

NFATC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.20799157).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278669.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFATC1	NM_001278669.2	MANE Select	c.37C>T	p.Pro13Ser	missense	Exon 1 of 10	NP_001265598.1	O95644-1
NFATC1	NM_006162.5		c.37C>T	p.Pro13Ser	missense	Exon 1 of 10	NP_006153.2
NFATC1	NM_172390.3		c.37C>T	p.Pro13Ser	missense	Exon 1 of 8	NP_765978.1	O95644-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.37C>T	p.Pro13Ser	missense	Exon 1 of 10	ENSP00000389377.2	O95644-1
NFATC1	ENST00000253506.9	TSL:1	c.37C>T	p.Pro13Ser	missense	Exon 1 of 10	ENSP00000253506.5	O95644-4
NFATC1	ENST00000591814.5	TSL:1	c.37C>T	p.Pro13Ser	missense	Exon 1 of 8	ENSP00000466194.1	O95644-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000224

AC:

AN:

1337924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663592

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27218

American (AMR)

AF:

0.00

AC:

AN:

34100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22348

East Asian (EAS)

AF:

0.00

AC:

AN:

29226

South Asian (SAS)

AF:

0.00

AC:

AN:

75258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4906

European-Non Finnish (NFE)

AF:

0.00000287

AC:

AN:

1044102

Other (OTH)

AF:

0.00

AC:

AN:

53434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0097

Eigen

Benign

0.041

Eigen_PC

Benign

0.047

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.13

PROVEAN

Benign

-0.42

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.059

Polyphen

0.98

Vest4

0.14

MutPred

0.14

Gain of glycosylation at P13 (P = 0.0172)

MVP

0.40

ClinPred

0.44

GERP RS

2.5

PromoterAI

-0.057

Neutral

(source)

Varity_R

0.21

gMVP

0.17

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over