16-28951127-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032815.4(NFATC2IP):​c.116C>T​(p.Ser39Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,393,942 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NFATC2IP
NM_032815.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.810
Variant links:
Genes affected
NFATC2IP (HGNC:25906): (nuclear factor of activated T cells 2 interacting protein) Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06322852).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFATC2IPNM_032815.4 linkc.116C>T p.Ser39Phe missense_variant Exon 1 of 8 ENST00000320805.9 NP_116204.3 Q8NCF5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NFATC2IPENST00000320805.9 linkc.116C>T p.Ser39Phe missense_variant Exon 1 of 8 1 NM_032815.4 ENSP00000324792.4 Q8NCF5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1393942
Hom.:
0
Cov.:
30
AF XY:
0.00000146
AC XY:
1
AN XY:
687144
show subpopulations
Gnomad4 AFR exome
AF:
0.0000641
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.116C>T (p.S39F) alteration is located in exon 1 (coding exon 1) of the NFATC2IP gene. This alteration results from a C to T substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.059
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.37
N
REVEL
Benign
0.033
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.055
T
Polyphen
0.010
B
Vest4
0.14
MutPred
0.18
Loss of phosphorylation at S39 (P = 0.0061);
MVP
0.17
MPC
0.29
ClinPred
0.22
T
GERP RS
2.0
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1
Varity_R
0.075
gMVP
0.080

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1964960631; hg19: chr16-28962448; API