16-69703943-G-C

Variant names:

• chr16-69703943-G-C
• rs2965757
• NM_138713.4:c.*7592G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138713.4(NFAT5):​c.*7592G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,454 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.092 (889 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: NFAT5 NM_138713.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 9 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]

ENSG00000260772 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

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.*7592G>C		3_prime_UTR	Exon 15 of 15	NP_619727.2	O94916-5
	NFAT5	NM_001113178.3		c.*7592G>C		3_prime_UTR	Exon 15 of 15	NP_001106649.1	O94916-4
	NFAT5	NM_006599.4		c.*7592G>C		3_prime_UTR	Exon 14 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.*7592G>C		3_prime_UTR	Exon 15 of 15	ENSP00000338806.3	O94916-5
	NFAT5	ENST00000354436.6	TSL:1	c.*7592G>C		3_prime_UTR	Exon 14 of 14	ENSP00000346420.2	O94916-1
	NFAT5	ENST00000393742.7	TSL:1	n.*12004G>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000377343.3	A0A499FIS8

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14001 AN: 151948 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.144 AC: 56 AN: 388 Hom.: 3 Cov.: 0 AF XY: 0.144 AC XY: 36 AN XY: 250

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.146 AC: 51 AN: 350

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.156 AC: 5 AN: 32

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0921 AC: 14004 AN: 152066 Hom.: 889 Cov.: 32 AF XY: 0.0944 AC XY: 7016 AN XY: 74304

African (AFR) AF: 0.0445 AC: 1846 AN: 41476

American (AMR) AF: 0.0498 AC: 760 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3470

East Asian (EAS) AF: 0.332 AC: 1717 AN: 5178

South Asian (SAS) AF: 0.118 AC: 569 AN: 4828

European-Finnish (FIN) AF: 0.139 AC: 1465 AN: 10556

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6779 AN: 67978

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

Alfa AF: 0.102 Hom.: 122

Bravo AF: 0.0841

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.61
PhyloP100		-0.041
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2965757; hg19: chr16-69737846;