NM_012153.6:c.52C>T

Variant names:

• chr11-34642682-C-T
• NM_012153.6:c.52C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012153.6(EHF):​c.52C>T​(p.Leu18Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EHF NM_012153.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2930747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012153.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHF	NM_012153.6	MANE Select	c.52C>T	p.Leu18Phe	missense	Exon 2 of 9	NP_036285.2
	EHF	NM_001206616.2		c.118C>T	p.Leu40Phe	missense	Exon 2 of 9	NP_001193545.1	Q9NZC4-3
	EHF	NM_001378052.1		c.118C>T	p.Leu40Phe	missense	Exon 2 of 9	NP_001364981.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHF	ENST00000257831.8	TSL:1 MANE Select	c.52C>T	p.Leu18Phe	missense	Exon 2 of 9	ENSP00000257831.3	Q9NZC4-1
	EHF	ENST00000531794.5	TSL:1	c.118C>T	p.Leu40Phe	missense	Exon 2 of 9	ENSP00000435835.1	Q9NZC4-3
	EHF	ENST00000530286.5	TSL:1	c.52C>T	p.Leu18Phe	missense	Exon 2 of 9	ENSP00000433508.1	Q9NZC4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.14
Sift	Benign	0.13	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.38		Loss of catalytic residue at L18 (P = 0.1043)
MVP		0.37
MPC		1.1
ClinPred		0.95	D
GERP RS		5.0
PromoterAI		0.022	Neutral
Varity_R		0.15
gMVP		0.26
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-34664229;