Genetic Variant NM_005702.4:c.489+145_489+147delTTT (chr17-28856714-CTTT-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+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

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+145_489+147delTTT	intron_variant	Intron 3 of 9	ENST00000254928.10	NP_005693.1	O75616-1
ERAL1	NM_001317985.2 link	c.486+148_486+150delTTT	intron_variant	Intron 3 of 9		NP_001304914.1	O75616
ERAL1	NM_001317986.2 link	c.489+145_489+147delTTT	intron_variant	Intron 3 of 8		NP_001304915.1	O75616
ERAL1	NR_134328.2 link	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 link	c.489+133_489+135delTTT		intron_variant	Intron 3 of 9	1	NM_005702.4	ENSP00000254928.5		O75616-1

Frequencies

GnomAD3 genomes

AF:

0.0000435

AC:

AN:

138038

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00295

AC XY:

718

AN XY:

243506

show subpopulations

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

African (AFR)

AF:

0.00231

AC:

AN:

11688

American (AMR)

AF:

0.00249

AC:

AN:

18064

Ashkenazi Jewish (ASJ)

AF:

0.00440

AC:

AN:

12494

East Asian (EAS)

AF:

0.00358

AC:

AN:

25694

South Asian (SAS)

AF:

0.00198

AC:

AN:

44370

European-Finnish (FIN)

AF:

0.00287

AC:

AN:

30366

Middle Eastern (MID)

AF:

0.00166

AC:

AN:

1812

European-Non Finnish (NFE)

AF:

0.00304

AC:

881

AN:

289526

Other (OTH)

AF:

0.00262

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.253

Heterozygous variant carriers

175

350

524

699

874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.0000435

AC:

AN:

138038

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

66890

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

37844

American (AMR)

AF:

0.0000731

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:

0.000371

AC:

AN:

8094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0000318

AC:

AN:

62922

Other (OTH)

AF:

0.00

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.267

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over