NM_005702.4:c.489+143_489+147delTTTTT

Variant names:

• chr17-28856714-CTTTTT-C
• rs372784089
• NM_005702.4:c.489+143_489+147delTTTTT

Variant summary

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

The NM_005702.4(ERAL1):​c.489+143_489+147delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 464,894 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: not found (cov: 30)
  • Exomes 𝑓: 0.000022 (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 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+143_489+147delTTTTT		intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.486+146_486+150delTTTTT		intron_variant	Intron 3 of 9		NP_001304914.1
ERAL1	NM_001317986.2	c.489+143_489+147delTTTTT		intron_variant	Intron 3 of 8		NP_001304915.1
ERAL1	NR_134328.2	n.508+143_508+147delTTTTT		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+137delTTTTT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000215 AC: 10 AN: 464894 Hom.: 0 AF XY: 0.0000202 AC XY: 5 AN XY: 247144

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

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: 12698

East Asian (EAS) AF: 0.00 AC: 0 AN: 26070

South Asian (SAS) AF: 0.0000221 AC: 1 AN: 45220

European-Finnish (FIN) AF: 0.0000974 AC: 3 AN: 30802

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

European-Non Finnish (NFE) AF: 0.0000170 AC: 5 AN: 293748

Other (OTH) AF: 0.0000411 AC: 1 AN: 24334

⚠️ 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 Cov.: 30

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;