rs372784089

Variant names:

• chr17-28856714-CTTTTTTTT-C
• rs372784089
• NM_005702.4:c.489+140_489+147delTTTTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr17-28856714-CTTTTTTTT-C
• chr17-28856714-CTTTTTTTT-CTTT
• chr17-28856714-CTTTTTTTT-CTTTT
• chr17-28856714-CTTTTTTTT-CTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTTTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTTTTTTTT
• chr17-28856714-CTTTTTTTT-CTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005702.4(ERAL1):​c.489+140_489+147delTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 138,074 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 0.000022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000026 (0 hom.)
  • Failed GnomAD Quality Control
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4	c.489+140_489+147delTTTTTTTT		intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.486+143_486+150delTTTTTTTT		intron_variant	Intron 3 of 9		NP_001304914.1
ERAL1	NM_001317986.2	c.489+140_489+147delTTTTTTTT		intron_variant	Intron 3 of 8		NP_001304915.1
ERAL1	NR_134328.2	n.508+140_508+147delTTTTTTTT		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+140delTTTTTTTT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes AF: 0.0000217 AC: 3 AN: 138074 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000264

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000318

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000258 AC: 12 AN: 464952 Hom.: 0 AF XY: 0.0000202 AC XY: 5 AN XY: 247164

African (AFR) AF: 0.00 AC: 0 AN: 11828

American (AMR) AF: 0.00 AC: 0 AN: 18364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12700

East Asian (EAS) AF: 0.00 AC: 0 AN: 26074

South Asian (SAS) AF: 0.00 AC: 0 AN: 45222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1830

European-Non Finnish (NFE) AF: 0.0000408 AC: 12 AN: 293778

Other (OTH) AF: 0.00 AC: 0 AN: 24344

GnomAD4 genome AF: 0.0000217 AC: 3 AN: 138074 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 66916

African (AFR) AF: 0.0000264 AC: 1 AN: 37844

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: 0.00 AC: 0 AN: 8104

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

European-Non Finnish (NFE) AF: 0.0000318 AC: 2 AN: 62946

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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;