rs542353221

Positions:

• chr16-69692513-TCAA-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The ENST00000349945.7(NFAT5):​c.2691_2693del​(p.Gln906del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00136 in 1,614,070 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q897Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (5 hom.)
• Consequence: NFAT5 ENST00000349945.7 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.82

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000349945.7
• BP6: Variant 16-69692513-TCAA-T is Benign according to our data. Variant chr16-69692513-TCAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 456657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.2691_2693del	p.Gln906del	inframe_deletion	13/15	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.2691_2693del	p.Gln906del	inframe_deletion	13/15	1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 175 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00136 AC: 342 AN: 250722 Hom.: 1 AF XY: 0.00152 AC XY: 206 AN XY: 135666

Gnomad AFR exome AF: 0.000437

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00378

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00310

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00139 AC: 2025 AN: 1461848 Hom.: 5 AF XY: 0.00140 AC XY: 1019 AN XY: 727224

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00436

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.00128 AC XY: 95 AN XY: 74416

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00199 Hom.: 0

Bravo AF: 0.000929

EpiCase AF: 0.00142

EpiControl AF: 0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

NFAT5-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Immunodeficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs542353221; hg19: chr16-69726416;