3-15436513-G-C

Variant names:

• chr3-15436513-G-C
• rs149438944
• NM_033083.7:c.698G>C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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]

EAF1-AS1 (HGNC:42328): (EAF1 antisense RNA 1)

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 rank	MANE	Protein	UniProt
EAF1	NM_033083.7	c.698G>C	p.Arg233Thr	missense_variant	Exon 5 of 6	ENST00000396842.7	NP_149074.3
EAF1	XM_011534165.2	c.395G>C	p.Arg132Thr	missense_variant	Exon 4 of 5		XP_011532467.1
EAF1	XM_011534166.2	c.395G>C	p.Arg132Thr	missense_variant	Exon 4 of 5		XP_011532468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EAF1	ENST00000396842.7	c.698G>C	p.Arg233Thr	missense_variant	Exon 5 of 6	1	NM_033083.7	ENSP00000380054.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

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.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

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: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0060	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.12
Sift	Benign	0.61	T
Sift4G	Benign	0.61	T
Polyphen		0.98	D
Vest4		0.62
MutPred		0.25		Gain of glycosylation at Y230 (P = 0.0022);
MVP		0.69
MPC		0.61
ClinPred		0.84	D
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

Other links and lift over

dbSNP: rs149438944; hg19: chr3-15478020;