11-34505716-G-A

Position:

• chr11-34505716-G-A

Variant summary

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

The NM_001422.4(ELF5):​c.34C>T​(p.Pro12Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELF5 NM_001422.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

Genes affected

ELF5 (HGNC:3320): (E74 like ETS transcription factor 5) This gene encodes an epithelium-specific ETS family transcription factor. In addition to its role in regulating the later stages of terminal differentiation of keratinocytes, it appears to regulate a number of epithelium-specific genes found in tissues containing glandular epithelium such as salivary gland and prostate. It has very low affinity to DNA due to its negative regulatory domain at the amino terminus. This gene has been implicated as a tumor suppressive transcription factor in breast cancer. [provided by RefSeq, May 2022]

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=0.19433072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF5	NM_001422.4	c.34C>T	p.Pro12Ser	missense_variant	2/7	ENST00000257832.7	NP_001413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF5	ENST00000257832.7	c.34C>T	p.Pro12Ser	missense_variant	2/7	1	NM_001422.4	ENSP00000257832	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Sep 01, 2021

The c.64C>T (p.P22S) alteration is located in exon 2 (coding exon 2) of the ELF5 gene. This alteration results from a C to T substitution at nucleotide position 64, causing the proline (P) at amino acid position 22 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.16	.;.;T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	.;.;N;.;.
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N;.;N;N;N
REVEL	Benign	0.066
Sift	Benign	0.068	T;.;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.0, 0.017	.;.;B;.;B
Vest4		0.21
MutPred		0.53		.;Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);.;.;
MVP		0.67
MPC		0.034
ClinPred		0.20	T
GERP RS		4.5
Varity_R		0.056
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-34527263;