NM_004451.5:c.348G>T

Variant names:

• chr11-64313973-G-T
• NM_004451.5:c.348G>T
• ESRRA p.Pro116Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004451.5(ESRRA):​c.348G>T​(p.Pro116Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ESRRA NM_004451.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-0.171 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRA	NM_004451.5	MANE Select	c.348G>T	p.Pro116Pro	synonymous	Exon 3 of 7	NP_004442.3
	ESRRA	NM_001282450.2		c.348G>T	p.Pro116Pro	synonymous	Exon 3 of 7	NP_001269379.1	P11474-1
	ESRRA	NM_001282451.2		c.348G>T	p.Pro116Pro	synonymous	Exon 3 of 7	NP_001269380.1	P11474-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRA	ENST00000000442.11	TSL:1 MANE Select	c.348G>T	p.Pro116Pro	synonymous	Exon 3 of 7	ENSP00000000442.6	P11474-1
	ESRRA	ENST00000406310.6	TSL:1	c.600G>T	p.Pro200Pro	synonymous	Exon 3 of 7	ENSP00000385971.2	A0A6E1WCP9
	ESRRA	ENST00000405666.5	TSL:1	c.348G>T	p.Pro116Pro	synonymous	Exon 3 of 7	ENSP00000384851.1	P11474-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.89
PhyloP100		-0.17
PromoterAI		0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-64081445; COSMIC: COSV50007529; COSMIC: COSV50007529;