13-40941071-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172373.4(ELF1):c.1106G>A(p.Arg369Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELF1 NM_172373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

Genes affected

ELF1 (HGNC:3316): (E74 like ETS transcription factor 1) This gene encodes an E26 transformation-specific related transcription factor. The encoded protein is primarily expressed in lymphoid cells and acts as both an enhancer and a repressor to regulate transcription of various genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ACMG classification

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=0.24869499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF1	NM_172373.4	c.1106G>A	p.Arg369Lys	missense_variant	8/9	ENST00000239882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF1	ENST00000239882.7	c.1106G>A	p.Arg369Lys	missense_variant	8/9	1	NM_172373.4	P1
ELF1	ENST00000635415.1	c.1106G>A	p.Arg369Lys	missense_variant	8/9	5
ELF1	ENST00000625359.1	c.1034G>A	p.Arg345Lys	missense_variant	7/8	2
ELF1	ENST00000498824.4	c.*849G>A		3_prime_UTR_variant, NMD_transcript_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Mar 23, 2022

The c.1106G>A (p.R369K) alteration is located in exon 8 (coding exon 7) of the ELF1 gene. This alteration results from a G to A substitution at nucleotide position 1106, causing the arginine (R) at amino acid position 369 to be replaced by a lysine (K). 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	0.095
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.53	N;.;.
REVEL	Benign	0.15
Sift	Benign	0.16	T;.;.
Sift4G	Benign	0.42	T;T;.
Polyphen		1.0	D;.;.
Vest4		0.59
MutPred		0.36		Gain of ubiquitination at R369 (P = 0.0039);.;Gain of ubiquitination at R369 (P = 0.0039);
MVP		0.53
MPC		0.68
ClinPred		0.76	D
GERP RS		5.6
Varity_R		0.24
gMVP		0.45

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.

Other links and lift over

hg19: chr13-41515207;