chr17-28856714-CT-C

Variant names:

• chr17-28856714-CT-C
• rs372784089
• NM_005702.4:c.489+147delT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005702.4(ERAL1):​c.489+147delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.22 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERAL1 NM_005702.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 17-28856714-CT-C is Benign according to our data. Variant chr17-28856714-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1288338.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4	c.489+147delT		intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.486+150delT		intron_variant	Intron 3 of 9		NP_001304914.1
ERAL1	NM_001317986.2	c.489+147delT		intron_variant	Intron 3 of 8		NP_001304915.1
ERAL1	NR_134328.2	n.508+147delT		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10	c.489+133delT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 273 AN: 137966 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00212

Gnomad ASJ AF: 0.00182

Gnomad EAS AF: 0.000419

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00199

Gnomad OTH AF: 0.00316

GnomAD2 exomes AF: 0.330 AC: 14451 AN: 43754 AF XY: 0.332

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.224 AC: 95180 AN: 424732 Hom.: 1 Cov.: 0 AF XY: 0.226 AC XY: 50822 AN XY: 225126

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.229 AC: 2448 AN: 10690

American (AMR) AF: 0.249 AC: 3929 AN: 15798

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 2686 AN: 11730

East Asian (EAS) AF: 0.239 AC: 5710 AN: 23904

South Asian (SAS) AF: 0.250 AC: 9669 AN: 38676

European-Finnish (FIN) AF: 0.214 AC: 6090 AN: 28508

Middle Eastern (MID) AF: 0.216 AC: 364 AN: 1684

European-Non Finnish (NFE) AF: 0.218 AC: 59099 AN: 271346

Other (OTH) AF: 0.232 AC: 5185 AN: 22396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00199 AC: 274 AN: 137960 Hom.: 0 Cov.: 30 AF XY: 0.00223 AC XY: 149 AN XY: 66874

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00108 AC: 41 AN: 37878

American (AMR) AF: 0.00212 AC: 29 AN: 13682

Ashkenazi Jewish (ASJ) AF: 0.00182 AC: 6 AN: 3292

East Asian (EAS) AF: 0.000420 AC: 2 AN: 4760

South Asian (SAS) AF: 0.000230 AC: 1 AN: 4352

European-Finnish (FIN) AF: 0.00792 AC: 64 AN: 8078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.00199 AC: 125 AN: 62886

Other (OTH) AF: 0.00315 AC: 6 AN: 1906

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs372784089; hg19: chr17-27183732;