rs2242345

Variant names:

• chr17-28858809-C-G
• rs2242345
• NM_005702.4:c.945C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-28858809-C-G
• chr17-28858809-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005702.4(ERAL1):​c.945C>G​(p.Asp315Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D315D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERAL1 NM_005702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 30 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35782814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4	c.945C>G	p.Asp315Glu	missense_variant	Exon 7 of 10	ENST00000254928.10	NP_005693.1
ERAL1	NM_001317985.2	c.942C>G	p.Asp314Glu	missense_variant	Exon 7 of 10		NP_001304914.1
ERAL1	NM_001317986.2	c.712-155C>G		intron_variant	Intron 6 of 8		NP_001304915.1
ERAL1	NR_134328.2	n.789-155C>G		intron_variant	Intron 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10	c.945C>G	p.Asp315Glu	missense_variant	Exon 7 of 10	1	NM_005702.4	ENSP00000254928.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.042	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.34
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.32
Sift	Benign	0.48	T
Sift4G	Benign	0.37	T
Polyphen		0.83	P
Vest4		0.091
MutPred		0.48		Gain of methylation at K317 (P = 0.0951);
MVP		0.82
MPC		0.23
ClinPred		0.46	T
GERP RS		2.5
PromoterAI		-0.020	Neutral
Varity_R		0.043
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2242345; hg19: chr17-27185827;