X-130067182-C-G

Position:

• chrX-130067182-C-G

Variant summary

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

The NM_001421.4(ELF4):​c.1531G>C​(p.Gly511Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ELF4 NM_001421.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.711

Genes affected

ELF4 (HGNC:3319): (E74 like ETS transcription factor 4) The protein encoded by this gene is a transcriptional activator that binds and activates the promoters of the CSF2, IL3, IL8, and PRF1 genes. The encoded protein is involved in natural killer cell development and function, innate immunity, and induction of cell cycle arrest in naive CD8+ cells. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Jan 2010]

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=0.13234487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF4	NM_001421.4	c.1531G>C	p.Gly511Arg	missense_variant	9/9	ENST00000308167.10	NP_001412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF4	ENST00000308167.10	c.1531G>C	p.Gly511Arg	missense_variant	9/9	1	NM_001421.4	ENSP00000311280.6
ELF4	ENST00000335997.11	c.1531G>C	p.Gly511Arg	missense_variant	9/9	1		ENSP00000338608.7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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

Sep 27, 2022

The c.1531G>C (p.G511R) alteration is located in exon 9 (coding exon 8) of the ELF4 gene. This alteration results from a G to C substitution at nucleotide position 1531, causing the glycine (G) at amino acid position 511 to be replaced by an arginine (R). 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	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T;T;T
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.85	.;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.028
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.044	D;D;D
Polyphen		0.70	P;P;.
Vest4		0.25
MutPred		0.26		Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);.;
MVP		0.17
MPC		0.46
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.23
gMVP		0.53

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: chrX-129201157;