Variant chr11-34493619-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001422.4(ELF5):c.215T>G(p.Leu72Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ELF5
NM_001422.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Variant links:

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]

ELF5 links:

ELF5 (HGNC:):

ELF5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF5	NM_001422.4 linkuse as main transcript	c.215T>G	p.Leu72Trp	missense_variant	3/7	ENST00000257832.7	NP_001413.1	Q9UKW6-2A8K443

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF5	ENST00000257832.7 linkuse as main transcript	c.215T>G	p.Leu72Trp	missense_variant	3/7	1	NM_001422.4	ENSP00000257832.3		Q9UKW6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2023

The c.245T>G (p.L82W) alteration is located in exon 3 (coding exon 3) of the ELF5 gene. This alteration results from a T to G substitution at nucleotide position 245, causing the leucine (L) at amino acid position 82 to be replaced by a tryptophan (W). 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

Pathogenic

0.76

BayesDel_addAF

Benign

0.0052

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Uncertain

0.44

.;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.87

D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.0

.;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

N;N;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.11

T;T;D

Polyphen

1.0

.;D;D

Vest4

0.74

MutPred

0.70

.;Loss of stability (P = 0.0261);.;

MVP

0.87

MPC

0.29

ClinPred

0.86

GERP RS

4.7

Varity_R

0.24

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over