Variant 11-64314317-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_004451.5(ESRRA):c.521G>A(p.Gly174Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,176 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: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ESRRA
NM_004451.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.670

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:

ESRRA (HGNC:):

ESRRA 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=0.18986827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRA	NM_004451.5 linkuse as main transcript	c.521G>A	p.Gly174Asp	missense_variant	4/7	ENST00000000442.11	NP_004442.3	P11474-1Q569H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRA	ENST00000000442.11 linkuse as main transcript	c.521G>A	p.Gly174Asp	missense_variant	4/7	1	NM_004451.5	ENSP00000000442.6		P11474-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723382

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 20, 2023

The c.521G>A (p.G174D) alteration is located in exon 4 (coding exon 3) of the ESRRA gene. This alteration results from a G to A substitution at nucleotide position 521, causing the glycine (G) at amino acid position 174 to be replaced by an aspartic acid (D). 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

0.28

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

.;T;.;T

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.0049

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.55

T;.;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

0.97

L;L;.;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.23

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.44

T;T;T;T

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.74

P;B;.;B

Vest4

0.24

MutPred

0.27

Loss of catalytic residue at G174 (P = 0.0537);Loss of catalytic residue at G174 (P = 0.0537);.;Loss of catalytic residue at G174 (P = 0.0537);

MVP

0.76

MPC

0.81

ClinPred

0.30

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

gMVP

0.77

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