11-34646453-T-C

Variant names:

• chr11-34646453-T-C
• NM_012153.6:c.112T>C

Variant summary

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

The NM_012153.6(EHF):​c.112T>C​(p.Phe38Leu) 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: 31)
• Consequence: EHF NM_012153.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

Genes affected

EHF (HGNC:3246): (ETS homologous factor) This gene encodes a protein that belongs to an ETS transcription factor subfamily characterized by epithelial-specific expression (ESEs). The encoded protein acts as a transcriptional repressor and may be involved in epithelial differentiation and carcinogenesis. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

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=0.21128184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHF	NM_012153.6	c.112T>C	p.Phe38Leu	missense_variant	Exon 3 of 9	ENST00000257831.8	NP_036285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHF	ENST00000257831.8	c.112T>C	p.Phe38Leu	missense_variant	Exon 3 of 9	1	NM_012153.6	ENSP00000257831.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178T>C (p.F60L) alteration is located in exon 3 (coding exon 3) of the EHF gene. This alteration results from a T to C substitution at nucleotide position 178, causing the phenylalanine (F) at amino acid position 60 to be replaced by a leucine (L). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T;.;T;T;.;.;.;.;T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	.;D;.;D;D;.;D;D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.40	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.15	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T;T;T;T;T;T
Polyphen		0.41	B;B;B;B;.;.;.;.;.;.
Vest4		0.33
MutPred		0.54		Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);.;Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP		0.55
MPC		0.82
ClinPred		0.57	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.27

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: chr11-34668000;