17-28856714-CTTTTTTTT-CTTTTT

Variant names:

• chr17-28856714-CTTT-C
• rs372784089
• NM_005702.4:c.489+145_489+147delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005702.4(ERAL1):​c.489+145_489+147delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 596,066 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0029 (0 hom.)
• Consequence: ERAL1 NM_005702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4	c.489+145_489+147delTTT		intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.486+148_486+150delTTT		intron_variant	Intron 3 of 9		NP_001304914.1
ERAL1	NM_001317986.2	c.489+145_489+147delTTT		intron_variant	Intron 3 of 8		NP_001304915.1
ERAL1	NR_134328.2	n.508+145_508+147delTTT		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10	c.489+133_489+135delTTT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes AF: 0.0000435 AC: 6 AN: 138038 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000731

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000371

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000318

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00363 AC: 159 AN: 43754 AF XY: 0.00408

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00320

Gnomad ASJ exome AF: 0.00759

Gnomad EAS exome AF: 0.00222

Gnomad FIN exome AF: 0.00410

Gnomad NFE exome AF: 0.00424

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00293 AC: 1341 AN: 458028 Hom.: 0 AF XY: 0.00295 AC XY: 718 AN XY: 243506

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

African (AFR) AF: 0.00231 AC: 27 AN: 11688

American (AMR) AF: 0.00249 AC: 45 AN: 18064

Ashkenazi Jewish (ASJ) AF: 0.00440 AC: 55 AN: 12494

East Asian (EAS) AF: 0.00358 AC: 92 AN: 25694

South Asian (SAS) AF: 0.00198 AC: 88 AN: 44370

European-Finnish (FIN) AF: 0.00287 AC: 87 AN: 30366

Middle Eastern (MID) AF: 0.00166 AC: 3 AN: 1812

European-Non Finnish (NFE) AF: 0.00304 AC: 881 AN: 289526

Other (OTH) AF: 0.00262 AC: 63 AN: 24014

⚠️ 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 AF: 0.0000435 AC: 6 AN: 138038 Hom.: 0 Cov.: 30 AF XY: 0.0000149 AC XY: 1 AN XY: 66890

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

African (AFR) AF: 0.00 AC: 0 AN: 37844

American (AMR) AF: 0.0000731 AC: 1 AN: 13684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3296

East Asian (EAS) AF: 0.00 AC: 0 AN: 4770

South Asian (SAS) AF: 0.00 AC: 0 AN: 4372

European-Finnish (FIN) AF: 0.000371 AC: 3 AN: 8094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000318 AC: 2 AN: 62922

Other (OTH) AF: 0.00 AC: 0 AN: 1904

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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;