Genetic Variant ERAL1:p.Asp315Asp (chr17-28858809-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005702.4(ERAL1):c.945C>T(p.Asp315Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,614,022 control chromosomes in the GnomAD database, including 504,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49618 hom., cov: 33)

Exomes 𝑓: 0.79 ( 454595 hom. )

Consequence

ERAL1
NM_005702.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.340

Variant links:

Genes affected

ERAL1 (HGNC:3424): (Era like 12S mitochondrial rRNA chaperone 1) The protein encoded by this gene is a GTPase that localizes to the mitochondrion. The encoded protein binds to the 3' terminal stem loop of 12S mitochondrial rRNA and is required for proper assembly of the 28S small mitochondrial ribosomal subunit. Deletion of this gene has been shown to cause mitochondrial dysfunction, growth retardation, and apoptosis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ERAL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-28858809-C-T is Benign according to our data. Variant chr17-28858809-C-T is described in ClinVar as [Benign]. Clinvar id is 1255389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4 link	c.945C>T	p.Asp315Asp	synonymous_variant	Exon 7 of 10	ENST00000254928.10	NP_005693.1	O75616-1
ERAL1	NM_001317985.2 link	c.942C>T	p.Asp314Asp	synonymous_variant	Exon 7 of 10		NP_001304914.1	O75616
ERAL1	NM_001317986.2 link	c.712-155C>T		intron_variant	Intron 6 of 8		NP_001304915.1	O75616
ERAL1	NR_134328.2 link	n.789-155C>T		intron_variant	Intron 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10 link	c.945C>T	p.Asp315Asp	synonymous_variant	Exon 7 of 10	1	NM_005702.4	ENSP00000254928.5		O75616-1

Frequencies

GnomAD3 genomes

AF:

0.805

AC:

122471

AN:

152048

Hom.:

49561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.869

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.801

Gnomad OTH

AF:

0.803

GnomAD3 exomes

AF:

0.772

AC:

193831

AN:

250924

Hom.:

75330

AF XY:

0.773

AC XY:

104909

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.866

Gnomad AMR exome

AF:

0.689

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.739

Gnomad SAS exome

AF:

0.690

Gnomad FIN exome

AF:

0.809

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.771

GnomAD4 exome

AF:

0.787

AC:

1150628

AN:

1461856

Hom.:

454595

Cov.:

AF XY:

0.785

AC XY:

570758

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.690

Gnomad4 ASJ exome

AF:

0.770

Gnomad4 EAS exome

AF:

0.654

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.811

Gnomad4 NFE exome

AF:

0.799

Gnomad4 OTH exome

AF:

0.792

GnomAD4 genome

AF:

0.806

AC:

122581

AN:

152166

Hom.:

49618

Cov.:

AF XY:

0.803

AC XY:

59762

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.869

Gnomad4 AMR

AF:

0.712

Gnomad4 ASJ

AF:

0.778

Gnomad4 EAS

AF:

0.733

Gnomad4 SAS

AF:

0.702

Gnomad4 FIN

AF:

0.813

Gnomad4 NFE

AF:

0.801

Gnomad4 OTH

AF:

0.803

Alfa

AF:

0.800

Hom.:

33920

Bravo

AF:

0.802

Asia WGS

AF:

0.735

AC:

2556

AN:

3478

EpiCase

AF:

0.804

EpiControl

AF:

0.810

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Perrault syndrome 6

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.4

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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