3-15434369-C-G

Variant summary

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

The NM_033083.7(EAF1):c.357C>G(p.Ile119Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EAF1 NM_033083.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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]

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

ACMG classification

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	UniProt
EAF1	NM_033083.7	c.357C>G	p.Ile119Met	missense_variant	4/6	ENST00000396842.7
EAF1	XM_011534165.2	c.54C>G	p.Ile18Met	missense_variant	3/5
EAF1	XM_011534166.2	c.54C>G	p.Ile18Met	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF1	ENST00000396842.7	c.357C>G	p.Ile119Met	missense_variant	4/6	1	NM_033083.7	P1
METTL6	ENST00000598878.1	c.-125+4809G>C		intron_variant		5
EAF1	ENST00000449565.1	c.*16C>G		3_prime_UTR_variant, NMD_transcript_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.357C>G (p.I119M) alteration is located in exon 4 (coding exon 4) of the EAF1 gene. This alteration results from a C to G substitution at nucleotide position 357, causing the isoleucine (I) at amino acid position 119 to be replaced by a methionine (M). 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	0.55
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.18	T
Polyphen		0.97	D
Vest4		0.61
MutPred		0.31		Gain of glycosylation at S116 (P = 0.0218);
MVP		0.50
MPC		1.1
ClinPred		0.94	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr3-15475876;