17-28858809-C-T

Variant names:

• chr17-28858809-C-T
• rs2242345
• NM_005702.4:c.945C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.340
• Publications: 30 publications found

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 Gene-Disease associations (from GenCC):

• Perrault syndrome 6

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Perrault syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.945C>T	p.Asp315Asp	synonymous_variant	Exon 7 of 10	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.942C>T	p.Asp314Asp	synonymous_variant	Exon 7 of 10		NP_001304914.1
ERAL1	NM_001317986.2	c.712-155C>T		intron_variant	Intron 6 of 8		NP_001304915.1
ERAL1	NR_134328.2	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	c.945C>T	p.Asp315Asp	synonymous_variant	Exon 7 of 10	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122471 AN: 152048 Hom.: 49561 Cov.: 33

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

GnomAD2 exomes AF: 0.772 AC: 193831 AN: 250924 AF XY: 0.773

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 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.: 73 AF XY: 0.785 AC XY: 570758 AN XY: 727232

African (AFR) AF: 0.864 AC: 28922 AN: 33480

American (AMR) AF: 0.690 AC: 30879 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 20133 AN: 26136

East Asian (EAS) AF: 0.654 AC: 25981 AN: 39698

South Asian (SAS) AF: 0.698 AC: 60198 AN: 86258

European-Finnish (FIN) AF: 0.811 AC: 43341 AN: 53410

Middle Eastern (MID) AF: 0.764 AC: 4404 AN: 5768

European-Non Finnish (NFE) AF: 0.799 AC: 888927 AN: 1111986

Other (OTH) AF: 0.792 AC: 47843 AN: 60396

GnomAD4 genome AF: 0.806 AC: 122581 AN: 152166 Hom.: 49618 Cov.: 33 AF XY: 0.803 AC XY: 59762 AN XY: 74404

African (AFR) AF: 0.869 AC: 36090 AN: 41532

American (AMR) AF: 0.712 AC: 10879 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2699 AN: 3468

East Asian (EAS) AF: 0.733 AC: 3794 AN: 5174

South Asian (SAS) AF: 0.702 AC: 3381 AN: 4818

European-Finnish (FIN) AF: 0.813 AC: 8611 AN: 10596

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54485 AN: 67982

Other (OTH) AF: 0.803 AC: 1700 AN: 2116

Alfa AF: 0.801 Hom.: 37937

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

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
PhyloP100		-0.34
PromoterAI		0.0071	Neutral
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2242345; hg19: chr17-27185827; COSMIC: COSV99650231; COSMIC: COSV99650231;