chr16-69626426-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_138713.4(NFAT5):ā€‹c.151A>Gā€‹(p.Lys51Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000695 in 1,583,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., cov: 31)
Exomes š‘“: 0.000069 ( 0 hom. )

Consequence

NFAT5
NM_138713.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 8.12
Variant links:
Genes affected
NFAT5 (HGNC:7774): (nuclear factor of activated T cells 5) The product of this gene is a member of the nuclear factors of activated T cells family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3308214).
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NFAT5NM_138713.4 linkuse as main transcriptc.151A>G p.Lys51Glu missense_variant 3/15 ENST00000349945.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NFAT5ENST00000349945.7 linkuse as main transcriptc.151A>G p.Lys51Glu missense_variant 3/151 NM_138713.4 A2O94916-5

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152172
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000350
AC:
8
AN:
228456
Hom.:
0
AF XY:
0.0000161
AC XY:
2
AN XY:
124524
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000632
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000655
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000692
AC:
99
AN:
1431124
Hom.:
0
Cov.:
30
AF XY:
0.0000534
AC XY:
38
AN XY:
712046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000264
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000855
Gnomad4 OTH exome
AF:
0.0000676
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152172
Hom.:
0
Cov.:
31
AF XY:
0.0000538
AC XY:
4
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000173
Hom.:
0
Bravo
AF:
0.0000718
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:2
Uncertain significance, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Uncertain significance, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.53
N;N;.
REVEL
Benign
0.18
Sift
Uncertain
0.0040
D;D;.
Sift4G
Benign
0.17
T;T;T
Polyphen
0.97
D;.;.
Vest4
0.52
MVP
0.50
ClinPred
0.43
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs141097482; hg19: chr16-69660329; API