Variant 3-15436513-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033083.7(EAF1):c.698G>C(p.Arg233Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

EAF1
NM_033083.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

EAF1 (HGNC:20907): (ELL associated factor 1) Enables transcription elongation regulator activity. Involved in regulation of transcription elongation from RNA polymerase II promoter. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

EAF1 links:

METTL6 (HGNC:28343): (methyltransferase 6, tRNA N3-cytidine) Enables enzyme binding activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

METTL6 links:

EAF1-AS1 (HGNC:):

EAF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EAF1	NM_033083.7 linkuse as main transcript	c.698G>C	p.Arg233Thr	missense_variant	5/6	ENST00000396842.7	NP_149074.3	Q96JC9-1
EAF1	XM_011534165.2 linkuse as main transcript	c.395G>C	p.Arg132Thr	missense_variant	4/5		XP_011532467.1	Q96JC9-2
EAF1	XM_011534166.2 linkuse as main transcript	c.395G>C	p.Arg132Thr	missense_variant	4/5		XP_011532468.1	Q96JC9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EAF1	ENST00000396842.7 linkuse as main transcript	c.698G>C	p.Arg233Thr	missense_variant	5/6	1	NM_033083.7	ENSP00000380054.2		Q96JC9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.698G>C (p.R233T) alteration is located in exon 5 (coding exon 5) of the EAF1 gene. This alteration results from a G to C substitution at nucleotide position 698, causing the arginine (R) at amino acid position 233 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.021

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

M_CAP

Benign

0.0060

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.46

PROVEAN

Benign

0.22

REVEL

Benign

0.12

Sift

Benign

0.61

Sift4G

Benign

0.61

Polyphen

0.98

Vest4

0.62

MutPred

0.25

Gain of glycosylation at Y230 (P = 0.0022);

MVP

0.69

MPC

0.61

ClinPred

0.84

GERP RS

4.0

Varity_R

0.15

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over