Variant 11-64314338-T-C 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_004451.5(ESRRA):c.542T>C(p.Leu181Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,594,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

ESRRA
NM_004451.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

ESRRA (HGNC:3471): (estrogen related receptor alpha) The protein encoded by this gene is a nuclear receptor that is most closely related to the estrogen receptor. This protein acts as a site-specific transcription factor and interacts with members of the PGC-1 family of transcription cofactors to regulate the expression of most genes involved in cellular energy production as well as in the process of mitochondrial biogenesis. A processed pseudogene of ESRRA is located on chromosome 13q12.1. [provided by RefSeq, Jun 2019]

ESRRA links:

Genome browser will be placed here

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=0.19749978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESRRA	NM_004451.5 linkuse as main transcript	c.542T>C	p.Leu181Pro	missense_variant	4/7	ENST00000000442.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRA	ENST00000000442.11 linkuse as main transcript	c.542T>C	p.Leu181Pro	missense_variant	4/7	1	NM_004451.5	P4	P11474-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

209024

Hom.:

AF XY:

0.0000351

AC XY:

AN XY:

114072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000367

Gnomad FIN exome

AF:

0.000111

Gnomad NFE exome

AF:

0.0000545

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000374

AC:

AN:

1442774

Hom.:

Cov.:

AF XY:

0.0000447

AC XY:

AN XY:

716010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000717

Gnomad4 FIN exome

AF:

0.000233

Gnomad4 NFE exome

AF:

0.0000299

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000581

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000584

AC:

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

Sep 01, 2021

The c.542T>C (p.L181P) alteration is located in exon 4 (coding exon 3) of the ESRRA gene. This alteration results from a T to C substitution at nucleotide position 542, causing the leucine (L) at amino acid position 181 to be replaced by a proline (P). 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

0.067

BayesDel_addAF

Benign

-0.0053

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.094

.;T;.;T

Eigen

Benign

-0.054

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.74

T;.;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.59

N;N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.059

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.019

B;B;.;B

Vest4

0.30

MVP

0.91

MPC

0.97

ClinPred

0.092

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.90

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