11-64314326-C-G

Position:

• chr11-64314326-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004451.5(ESRRA):​c.530C>G​(p.Pro177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ESRRA NM_004451.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68

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]

ACMG classification

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=0.24937394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESRRA	NM_004451.5	c.530C>G	p.Pro177Arg	missense_variant	4/7	ENST00000000442.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRA	ENST00000000442.11	c.530C>G	p.Pro177Arg	missense_variant	4/7	1	NM_004451.5	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.530C>G (p.P177R) alteration is located in exon 4 (coding exon 3) of the ESRRA gene. This alteration results from a C to G substitution at nucleotide position 530, causing the proline (P) at amino acid position 177 to be replaced by an arginine (R). 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	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.;T
Eigen	Benign	0.077
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;.;T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.3	L;L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.59	N;N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.23	B;D;.;D
Vest4		0.41
MutPred		0.28		Gain of methylation at P177 (P = 0.0174);Gain of methylation at P177 (P = 0.0174);.;Gain of methylation at P177 (P = 0.0174);
MVP		0.77
MPC		0.66
ClinPred		0.49	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64081798;