17-28856714-CTTTTTTTT-CTTTTTTTTTT

Variant names:

• chr17-28856714-C-CTT
• rs372784089
• NM_005702.4:c.489+146_489+147dupTT

Variant summary

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

The NM_005702.4(ERAL1):​c.489+146_489+147dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 599,064 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 0.000029 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: ERAL1 NM_005702.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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+146_489+147dupTT		intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.486+149_486+150dupTT		intron_variant	Intron 3 of 9		NP_001304914.1
ERAL1	NM_001317986.2	c.489+146_489+147dupTT		intron_variant	Intron 3 of 8		NP_001304915.1
ERAL1	NR_134328.2	n.508+146_508+147dupTT		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10	c.489+132_489+133insTT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes AF: 0.0000290 AC: 4 AN: 138072 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000477

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000983 AC: 43 AN: 43754 AF XY: 0.00101

Gnomad AFR exome AF: 0.000292

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.000404

Gnomad FIN exome AF: 0.000821

Gnomad NFE exome AF: 0.00137

Gnomad OTH exome AF: 0.000735

GnomAD4 exome AF: 0.00222 AC: 1023 AN: 460992 Hom.: 0 Cov.: 0 AF XY: 0.00221 AC XY: 541 AN XY: 245020

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

African (AFR) AF: 0.00247 AC: 29 AN: 11730

American (AMR) AF: 0.00203 AC: 37 AN: 18218

Ashkenazi Jewish (ASJ) AF: 0.00199 AC: 25 AN: 12558

East Asian (EAS) AF: 0.00205 AC: 53 AN: 25834

South Asian (SAS) AF: 0.00105 AC: 47 AN: 44920

European-Finnish (FIN) AF: 0.00209 AC: 64 AN: 30596

Middle Eastern (MID) AF: 0.00276 AC: 5 AN: 1810

European-Non Finnish (NFE) AF: 0.00243 AC: 708 AN: 291214

Other (OTH) AF: 0.00228 AC: 55 AN: 24112

⚠️ 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: 0.0000290 AC: 4 AN: 138072 Hom.: 0 Cov.: 30 AF XY: 0.0000299 AC XY: 2 AN XY: 66916

⚠️ 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: 37842

American (AMR) AF: 0.00 AC: 0 AN: 13686

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: 0.000123 AC: 1 AN: 8104

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

European-Non Finnish (NFE) AF: 0.0000477 AC: 3 AN: 62946

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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs372784089; hg19: chr17-27183732;