Variant 3-15427796-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033083.7(EAF1):c.17A>G(p.Asn6Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000067 in 1,551,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

EAF1
NM_033083.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12465143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EAF1	NM_033083.7 linkuse as main transcript	c.17A>G	p.Asn6Ser	missense_variant	1/6	ENST00000396842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF1	ENST00000396842.7 linkuse as main transcript	c.17A>G	p.Asn6Ser	missense_variant	1/6	1	NM_033083.7	P1	Q96JC9-1
METTL6	ENST00000598878.1 linkuse as main transcript	c.-124-1161T>C		intron_variant		5
EAF1	ENST00000449565.1 linkuse as main transcript	c.17A>G	p.Asn6Ser	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152094

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:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000388

AC:

AN:

154464

Hom.:

AF XY:

0.0000246

AC XY:

AN XY:

81434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000533

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000722

AC:

101

AN:

1399034

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

690046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Sep 25, 2023

The c.17A>G (p.N6S) 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 17, causing the asparagine (N) at amino acid position 6 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.032

Eigen

Benign

-0.096

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.056

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.79

REVEL

Benign

0.27

Sift

Benign

0.47

Sift4G

Benign

0.67

Polyphen

0.031

Vest4

0.20

MutPred

0.44

Loss of glycosylation at T4 (P = 0.0581);

MVP

0.71

MPC

0.34

ClinPred

0.16

GERP RS

5.0

Varity_R

0.15

gMVP

0.40

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