chr16-68122800-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_173165.3(NFATC3):c.917C>T(p.Thr306Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000014 ( 1 hom. )
Consequence
NFATC3
NM_173165.3 missense
NM_173165.3 missense
Scores
4
6
4
Clinical Significance
Conservation
PhyloP100: 7.50
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFATC3 | NM_173165.3 | c.917C>T | p.Thr306Ile | missense_variant | 2/10 | ENST00000346183.8 | |
NFATC3 | NM_004555.4 | c.917C>T | p.Thr306Ile | missense_variant | 2/11 | ||
NFATC3 | NM_173163.3 | c.917C>T | p.Thr306Ile | missense_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFATC3 | ENST00000346183.8 | c.917C>T | p.Thr306Ile | missense_variant | 2/10 | 1 | NM_173165.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152272Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251446Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135894
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461894Hom.: 1 Cov.: 35 AF XY: 0.0000110 AC XY: 8AN XY: 727248
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152272Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74392
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | The c.917C>T (p.T306I) alteration is located in exon 2 (coding exon 2) of the NFATC3 gene. This alteration results from a C to T substitution at nucleotide position 917, causing the threonine (T) at amino acid position 306 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0, 1.0
.;D;D;.
Vest4
MutPred
Loss of disorder (P = 0.0312);Loss of disorder (P = 0.0312);Loss of disorder (P = 0.0312);Loss of disorder (P = 0.0312);
MVP
MPC
0.44
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at