Variant 19-17236011-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005234.4(NR2F6):c.428C>T(p.Ser143Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000283 in 1,414,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

NR2F6
NM_005234.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

NR2F6 (HGNC:7977): (nuclear receptor subfamily 2 group F member 6) Enables DNA-binding transcription factor activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NR2F6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19558963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F6	NM_005234.4 linkuse as main transcript	c.428C>T	p.Ser143Leu	missense_variant	3/4	ENST00000291442.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F6	ENST00000291442.4 linkuse as main transcript	c.428C>T	p.Ser143Leu	missense_variant	3/4	1	NM_005234.4	P1
NR2F6	ENST00000596878.1 linkuse as main transcript	c.68C>T	p.Ser23Leu	missense_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.90e-7

AC:

AN:

1265508

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

623004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000357

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149050

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72786

show subpopulations

Gnomad4 AFR

AF:

0.0000495

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.428C>T (p.S143L) alteration is located in exon 3 (coding exon 3) of the NR2F6 gene. This alteration results from a C to T substitution at nucleotide position 428, causing the serine (S) at amino acid position 143 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.54

T;T;T

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.

MutationTaster

Benign

0.83

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.7

N;.;.

REVEL

Benign

0.024

Sift

Benign

0.27

T;.;.

Sift4G

Benign

0.23

T;.;.

Polyphen

0.55

P;.;.

Vest4

0.20

MutPred

0.35

Loss of glycosylation at S143 (P = 0.0014);.;.;

MVP

0.24

MPC

1.1

ClinPred

0.68

GERP RS

1.6

Varity_R

0.10

gMVP

0.22

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