Variant 3-15429988-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033083.7(EAF1):c.179T>C(p.Ile60Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,602 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: 0.0000014 ( 0 hom. )

Consequence

EAF1
NM_033083.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EAF1	NM_033083.7 linkuse as main transcript	c.179T>C	p.Ile60Thr	missense_variant	2/6	ENST00000396842.7	NP_149074.3
EAF1	XM_011534165.2 linkuse as main transcript	c.13T>C	p.Leu5=	synonymous_variant	2/5		XP_011532467.1
EAF1	XM_011534166.2 linkuse as main transcript	c.13T>C	p.Leu5=	synonymous_variant	2/5		XP_011532468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EAF1	ENST00000396842.7 linkuse as main transcript	c.179T>C	p.Ile60Thr	missense_variant	2/6	1	NM_033083.7	ENSP00000380054	P1	Q96JC9-1
METTL6	ENST00000598878.1 linkuse as main transcript	c.-124-3353A>G		intron_variant		5		ENSP00000471485
EAF1	ENST00000449565.1 linkuse as main transcript	c.179T>C	p.Ile60Thr	missense_variant, NMD_transcript_variant	2/5	2		ENSP00000399636

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725126

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 17, 2023

The c.179T>C (p.I60T) alteration is located in exon 2 (coding exon 2) of the EAF1 gene. This alteration results from a T to C substitution at nucleotide position 179, causing the isoleucine (I) at amino acid position 60 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.97

MutPred

0.72

Loss of stability (P = 0.0039);

MVP

0.89

MPC

1.2

ClinPred

1.0

GERP RS

5.8

Varity_R

0.64

gMVP

0.75

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over