16-68122295-C-T

Position:

chr16-68122295-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_173165.3(NFATC3):c.412C>T(p.Arg138Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,614,064 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 34 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

NFATC3
NM_173165.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

NFATC3 (HGNC:7777): (nuclear factor of activated T cells 3) The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Nov 2010]

NFATC3 links:

ENSG00000261864 (HGNC:):

ENSG00000261864 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033489466).

BP6

Variant 16-68122295-C-T is Benign according to our data. Variant chr16-68122295-C-T is described in ClinVar as [Benign]. Clinvar id is 788366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1618/152194) while in subpopulation AFR AF= 0.0372 (1546/41518). AF 95% confidence interval is 0.0357. There are 34 homozygotes in gnomad4. There are 774 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1618 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC3	NM_173165.3 link	c.412C>T	p.Arg138Trp	missense_variant	2/10	ENST00000346183.8	NP_775188.1	Q12968-1B5B2S1
NFATC3	NM_004555.4 link	c.412C>T	p.Arg138Trp	missense_variant	2/11		NP_004546.1	Q12968-2B5B2S0
NFATC3	NM_173163.3 link	c.412C>T	p.Arg138Trp	missense_variant	2/11		NP_775186.1	Q12968-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC3	ENST00000346183.8 link	c.412C>T	p.Arg138Trp	missense_variant	2/10	1	NM_173165.3	ENSP00000300659.5		Q12968-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1615

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00272

AC:

684

AN:

251088

Hom.:

AF XY:

0.00200

AC XY:

272

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0387

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.00108

AC:

1577

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000935

AC XY:

680

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0378

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000962

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.0106

AC:

1618

AN:

152194

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

774

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0372

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.0121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0355

AC:

156

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00345

AC:

419

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;.;T;.

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

D;D;D;D

MetaRNN

Benign

0.0033

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

.;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.015

.;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.99, 0.99

.;D;D;.

Vest4

0.30

MVP

0.15

MPC

0.20

ClinPred

0.027

GERP RS

3.0

Varity_R

0.053

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over