11-34646485-G-C

Position:

• chr11-34646485-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012153.6(EHF):​c.144G>C​(p.Gln48His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 4.70

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHF	NM_012153.6	c.144G>C	p.Gln48His	missense_variant	3/9	ENST00000257831.8	NP_036285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHF	ENST00000257831.8	c.144G>C	p.Gln48His	missense_variant	3/9	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.210G>C (p.Q70H) alteration is located in exon 3 (coding exon 3) of the EHF gene. This alteration results from a G to C substitution at nucleotide position 210, causing the glutamine (Q) at amino acid position 70 to be replaced by a histidine (H). 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	0.47
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T;.;T;T;.;.;.;.;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	.;D;.;D;D;.;D;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.75	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;M;M;M;.;.;.;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D;N;D;D;D;D;D;D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;.;.;.;.;.
Vest4		0.73
MutPred		0.54		Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);.;Loss of solvent accessibility (P = 0.0152);Loss of solvent accessibility (P = 0.0152);
MVP		0.79
MPC		1.2
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.61
gMVP		0.54

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: chr11-34668032;