Genetic Variant ENTR1:p.Ile311Asn (chr9-136405164-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039707.2(ENTR1):c.932T>A(p.Ile311Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I311T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ENTR1
NM_001039707.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63

Publications

0 publications found

Variant links:

Genes affected

ENTR1 (HGNC:10667): (endosome associated trafficking regulator 1) Involved in several processes, including endocytic recycling; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in endosome; microtubule organizing center; and midbody. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ENTR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.27045172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039707.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTR1	NM_001039707.2	MANE Select	c.932T>A	p.Ile311Asn	missense	Exon 7 of 10	NP_001034796.1	Q96C92-1
ENTR1	NM_006643.4		c.863T>A	p.Ile288Asn	missense	Exon 6 of 9	NP_006634.3
ENTR1	NM_001039708.2		c.713T>A	p.Ile238Asn	missense	Exon 5 of 8	NP_001034797.1	Q96C92-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTR1	ENST00000357365.8	TSL:5 MANE Select	c.932T>A	p.Ile311Asn	missense	Exon 7 of 10	ENSP00000349929.3	Q96C92-1
ENTR1	ENST00000298537.11	TSL:1	c.863T>A	p.Ile288Asn	missense	Exon 6 of 9	ENSP00000298537.7	Q96C92-2
ENTR1	ENST00000918209.1		c.1148T>A	p.Ile383Asn	missense	Exon 7 of 10	ENSP00000588268.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.045

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

PhyloP100

2.6

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.89

REVEL

Benign

0.027

Sift

Benign

0.25

Sift4G

Uncertain

0.0060

Polyphen

0.37

Vest4

0.57

MutPred

0.32

Gain of ubiquitination at K309 (P = 0.0438)

MVP

0.83

MPC

0.021

ClinPred

0.16

GERP RS

3.4

Varity_R

0.16

gMVP

0.18

Mutation Taster

=78/22

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over