rs542353221

Variant names:

• chr16-69692513-TCAA-T
• rs542353221
• NM_138713.4:c.2691_2693delACA

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_138713.4(NFAT5):​c.2691_2693delACA​(p.Gln898del) variant causes a disruptive 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 NM_138713.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.82
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_138713.4
• 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 VariationId is 456657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 174 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138713.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	NM_138713.4	MANE Select	c.2691_2693delACA	p.Gln898del	disruptive_inframe_deletion	Exon 13 of 15	NP_619727.2	O94916-5
	NFAT5	NM_001113178.3		c.2688_2690delACA	p.Gln897del	disruptive_inframe_deletion	Exon 13 of 15	NP_001106649.1	O94916-4
	NFAT5	NM_006599.4		c.2637_2639delACA	p.Gln880del	disruptive_inframe_deletion	Exon 12 of 14	NP_006590.1	O94916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	ENST00000349945.7	TSL:1 MANE Select	c.2691_2693delACA	p.Gln898del	disruptive_inframe_deletion	Exon 13 of 15	ENSP00000338806.3	O94916-5
	NFAT5	ENST00000567239.5	TSL:1	c.2688_2690delACA	p.Gln897del	disruptive_inframe_deletion	Exon 13 of 15	ENSP00000457593.1	O94916-4
	NFAT5	ENST00000354436.6	TSL:1	c.2637_2639delACA	p.Gln880del	disruptive_inframe_deletion	Exon 12 of 14	ENSP00000346420.2	O94916-1

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

GnomAD2 exomes AF: 0.00136 AC: 342 AN: 250722 AF XY: 0.00152

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 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

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00436 AC: 114 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00264 AC: 141 AN: 53396

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.00147 AC: 1633 AN: 1111992

Other (OTH) AF: 0.00167 AC: 101 AN: 60394

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

African (AFR) AF: 0.000313 AC: 13 AN: 41520

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 68002

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00199 Hom.: 0

Bravo AF: 0.000929

EpiCase AF: 0.00142

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency (1)
-	-	1	NFAT5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs542353221; hg19: chr16-69726416; COSMIC: COSV100590646; COSMIC: COSV100590646;