rs774263990

Variant names:

• chr16-69693665-GCAA-G
• rs774263990
• NM_138713.4:c.3849_3851delACA

Your query was ambiguous. Multiple possible variants found:

• chr16-69693665-GCAA-G
• chr16-69693665-GCAA-GCAACAA

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_138713.4(NFAT5):​c.3849_3851delACA​(p.Gln1284del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000163 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q1283Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: NFAT5 NM_138713.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.82
• Publications: 0 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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_138713.4
• BP6: Variant 16-69693665-GCAA-G is Benign according to our data. Variant chr16-69693665-GCAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 456660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 19 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.3849_3851delACA	p.Gln1284del	disruptive_inframe_deletion	Exon 13 of 15	NP_619727.2	O94916-5
	NFAT5	NM_001113178.3		c.3846_3848delACA	p.Gln1283del	disruptive_inframe_deletion	Exon 13 of 15	NP_001106649.1	O94916-4
	NFAT5	NM_006599.4		c.3795_3797delACA	p.Gln1266del	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.3849_3851delACA	p.Gln1284del	disruptive_inframe_deletion	Exon 13 of 15	ENSP00000338806.3	O94916-5
	NFAT5	ENST00000567239.5	TSL:1	c.3846_3848delACA	p.Gln1283del	disruptive_inframe_deletion	Exon 13 of 15	ENSP00000457593.1	O94916-4
	NFAT5	ENST00000354436.6	TSL:1	c.3795_3797delACA	p.Gln1266del	disruptive_inframe_deletion	Exon 12 of 14	ENSP00000346420.2	O94916-1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 251188 AF XY: 0.000169

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 244 AN: 1461866 Hom.: 0 AF XY: 0.000190 AC XY: 138 AN XY: 727230

African (AFR) AF: 0.000179 AC: 6 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000203 AC: 226 AN: 1112008

Other (OTH) AF: 0.000166 AC: 10 AN: 60394

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74456

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8
Mutation Taster		=83/17	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs774263990;

hg19: chr16-69727568;