dbSNP rs375623778: ELAC1:p.Arg100Trp (chr18-50984236-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018696.3(ELAC1):c.298C>T(p.Arg100Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ELAC1
NM_018696.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.337

Publications

2 publications found

Variant links:

Genes affected

ELAC1 (HGNC:14197): (elaC ribonuclease Z 1) Predicted to enable 3'-tRNA processing endoribonuclease activity. Predicted to be involved in tRNA 3'-trailer cleavage, endonucleolytic. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ELAC1 links:

ENSG00000267699 (HGNC:):

ENSG00000267699 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.857

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018696.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC1	NM_018696.3	MANE Select	c.298C>T	p.Arg100Trp	missense	Exon 3 of 4	NP_061166.1	Q9H777

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELAC1	ENST00000269466.8	TSL:1 MANE Select	c.298C>T	p.Arg100Trp	missense	Exon 3 of 4	ENSP00000269466.3	Q9H777
ELAC1	ENST00000591429.1	TSL:1	c.298C>T	p.Arg100Trp	missense	Exon 3 of 3	ENSP00000464770.1	K7EIJ1
ENSG00000267699	ENST00000590722.2	TSL:2	n.157+9675C>T		intron	N/A	ENSP00000465737.1	E7EUB6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251402

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000531

AC:

AN:

1112006

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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

Cov.:

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.094

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.29

MutationAssessor

Pathogenic

3.4

PhyloP100

0.34

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.94

MVP

0.60

MPC

0.45

ClinPred

0.92

GERP RS

6.2

Varity_R

0.78

gMVP

0.83

Mutation Taster

=25/75

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over