11-34490028-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001422.4(ELF5):​c.387C>G​(p.Ser129Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ELF5
NM_001422.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.160
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]

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ACMG classification

Classification made for transcript

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=0.18983203).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ELF5NM_001422.4 linkuse as main transcriptc.387C>G p.Ser129Arg missense_variant 4/7 ENST00000257832.7 NP_001413.1 Q9UKW6-2A8K443

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ELF5ENST00000257832.7 linkuse as main transcriptc.387C>G p.Ser129Arg missense_variant 4/71 NM_001422.4 ENSP00000257832.3 Q9UKW6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsOct 25, 2024The c.417C>G (p.S139R) alteration is located in exon 4 (coding exon 4) of the ELF5 gene. This alteration results from a C to G substitution at nucleotide position 417, causing the serine (S) at amino acid position 139 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
0.19
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.24
.;.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;.;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.96
N;.;N
REVEL
Benign
0.0060
Sift
Uncertain
0.010
D;.;D
Sift4G
Benign
0.45
T;T;T
Polyphen
0.010
.;.;B
Vest4
0.39
MutPred
0.32
.;.;Gain of solvent accessibility (P = 0.0365);
MVP
0.53
MPC
0.034
ClinPred
0.20
T
GERP RS
3.5
Varity_R
0.13
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755990303; hg19: chr11-34511575; API