dbSNP rs1020176693: NFATC2IP:p.Ile58Thr (chr16-28951184-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032815.4(NFATC2IP):c.173T>C(p.Ile58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,389,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I58L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

NFATC2IP
NM_032815.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

Publications

0 publications found

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]

NFATC2IP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025966465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032815.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NFATC2IP	NM_032815.4	MANE Select	c.173T>C	p.Ile58Thr	missense	Exon 1 of 8	NP_116204.3
NFATC2IP	NM_001394784.1		c.173T>C	p.Ile58Thr	missense	Exon 1 of 7	NP_001381713.1
NFATC2IP	NM_001394785.1		c.173T>C	p.Ile58Thr	missense	Exon 1 of 6	NP_001381714.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFATC2IP	ENST00000320805.9	TSL:1 MANE Select	c.173T>C	p.Ile58Thr	missense	Exon 1 of 8	ENSP00000324792.4	Q8NCF5-1
NFATC2IP	ENST00000564978.5	TSL:1	c.-65+350T>C		intron	N/A	ENSP00000456948.1	H3BSZ7
NFATC2IP	ENST00000895633.1		c.173T>C	p.Ile58Thr	missense	Exon 1 of 6	ENSP00000565692.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000228

AC:

AN:

144430

AF XY:

0.000193

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000244

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1389070

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

684262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30798

American (AMR)

AF:

0.00103

AC:

AN:

35108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24854

East Asian (EAS)

AF:

0.00

AC:

AN:

35080

South Asian (SAS)

AF:

0.00

AC:

AN:

78418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1073770

Other (OTH)

AF:

0.0000174

AC:

AN:

57518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.090

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.71

M_CAP

Benign

0.0074

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.26

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.48

REVEL

Benign

0.022

Sift

Benign

0.049

Sift4G

Benign

0.14

Polyphen

0.42

Vest4

0.12

MutPred

0.26

Gain of sheet (P = 0.0043)

MVP

0.16

MPC

0.42

ClinPred

0.025

GERP RS

1.9

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.13

Mutation Taster

=98/2

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