Genetic Variant NM_005702.4:c.489+144_489+147delTTTT (chr17-28856714-CTTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_005702.4(ERAL1):c.489+144_489+147delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 463,852 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 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ERAL1
NM_005702.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

0 publications found

Variant links:

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

ERAL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4 link	c.489+144_489+147delTTTT	intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1	O75616-1
ERAL1	NM_001317985.2 link	c.486+147_486+150delTTTT	intron_variant	Intron 3 of 9		NP_001304914.1	O75616
ERAL1	NM_001317986.2 link	c.489+144_489+147delTTTT	intron_variant	Intron 3 of 8		NP_001304915.1	O75616
ERAL1	NR_134328.2 link	n.508+144_508+147delTTTT	intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10 link	c.489+133_489+136delTTTT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5		O75616-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138070

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000276

AC:

128

AN:

463852

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

246610

show subpopulations

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

African (AFR)

AF:

0.000339

AC:

AN:

11798

American (AMR)

AF:

0.000382

AC:

AN:

18326

Ashkenazi Jewish (ASJ)

AF:

0.000237

AC:

AN:

12668

East Asian (EAS)

AF:

0.000231

AC:

AN:

26012

South Asian (SAS)

AF:

0.000266

AC:

AN:

45126

European-Finnish (FIN)

AF:

0.000326

AC:

AN:

30714

Middle Eastern (MID)

AF:

0.00165

AC:

AN:

1822

European-Non Finnish (NFE)

AF:

0.000270

AC:

AN:

293100

Other (OTH)

AF:

0.000165

AC:

AN:

24286

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.242

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

138070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66914

African (AFR)

AF:

0.00

AC:

AN:

37844

American (AMR)

AF:

0.00

AC:

AN:

13684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

4770

South Asian (SAS)

AF:

0.00

AC:

AN:

4372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62946

Other (OTH)

AF:

0.00

AC:

AN:

1904

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over