Genetic Variant ENTHD1:p.Leu427Ser (chr22-39744223-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152512.4(ENTHD1):c.1280T>C(p.Leu427Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ENTHD1
NM_152512.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.208

Publications

0 publications found

Variant links:

Genes affected

ENTHD1 (HGNC:26352): (ENTH domain containing 1) Predicted to enable clathrin binding activity and phospholipid binding activity. Predicted to be involved in endocytosis. Predicted to be part of clathrin vesicle coat. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012440234).

BP6

Variant 22-39744223-A-G is Benign according to our data. Variant chr22-39744223-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3845024.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152512.4. 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
	ENTHD1	NM_152512.4	MANE Select	c.1280T>C	p.Leu427Ser	missense	Exon 7 of 7	NP_689725.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTHD1	ENST00000325157.7	TSL:1 MANE Select	c.1280T>C	p.Leu427Ser	missense	Exon 7 of 7	ENSP00000317431.6	Q8IYW4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250782

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111862

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.40

M_CAP

Benign

0.0021

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.12

PhyloP100

0.21

PrimateAI

Benign

0.23

PROVEAN

Benign

0.99

REVEL

Benign

0.040

Sift

Benign

0.56

Sift4G

Benign

0.41

Polyphen

0.0030

Vest4

0.045

MVP

0.055

MPC

0.091

ClinPred

0.019

GERP RS

-4.6

Varity_R

0.036

gMVP

0.039

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over