Variant 3-15427820-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000396842.7(EAF1):c.41A>G(p.His14Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,551,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

EAF1
ENST00000396842.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.52

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:

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.41A>G	p.His14Arg	missense_variant	1/6	ENST00000396842.7	NP_149074.3	Q96JC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EAF1	ENST00000396842.7 linkuse as main transcript	c.41A>G	p.His14Arg	missense_variant	1/6	1	NM_033083.7	ENSP00000380054.2	Q96JC9-1
METTL6	ENST00000598878.1 linkuse as main transcript	c.-124-1185T>C		intron_variant		5		ENSP00000471485.1	M0R0W0
EAF1	ENST00000449565.1 linkuse as main transcript	n.41A>G		non_coding_transcript_exon_variant	1/5	2		ENSP00000399636.1	F8WFA5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152104

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

154094

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81238

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000342

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1399024

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000556

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000308

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

Jun 28, 2023

The c.41A>G (p.H14R) alteration is located in exon 1 (coding exon 1) of the EAF1 gene. This alteration results from a A to G substitution at nucleotide position 41, causing the histidine (H) at amino acid position 14 to be replaced by an arginine (R). 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

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.61

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.090

REVEL

Uncertain

0.34

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.99

Vest4

0.64

MutPred

0.69

Gain of disorder (P = 0.0455);

MVP

0.56

MPC

0.72

ClinPred

0.49

GERP RS

5.0

Varity_R

0.28

gMVP

0.86

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