Genetic Variant NM_001039707.2:c.932T>C (chr9-136405164-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039707.2(ENTR1):c.932T>C(p.Ile311Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ENTR1
NM_001039707.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18847987).

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>C	p.Ile311Thr	missense	Exon 7 of 10	NP_001034796.1	Q96C92-1
ENTR1	NM_006643.4		c.863T>C	p.Ile288Thr	missense	Exon 6 of 9	NP_006634.3
ENTR1	NM_001039708.2		c.713T>C	p.Ile238Thr	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>C	p.Ile311Thr	missense	Exon 7 of 10	ENSP00000349929.3	Q96C92-1
ENTR1	ENST00000298537.11	TSL:1	c.863T>C	p.Ile288Thr	missense	Exon 6 of 9	ENSP00000298537.7	Q96C92-2
ENTR1	ENST00000918209.1		c.1148T>C	p.Ile383Thr	missense	Exon 7 of 10	ENSP00000588268.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111932

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.24

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.011

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.037

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.94

PhyloP100

2.6

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.98

REVEL

Benign

0.075

Sift

Benign

0.19

Sift4G

Uncertain

0.027

Polyphen

0.93

Vest4

0.40

MutPred

0.33

Loss of stability (P = 0.0184)

MVP

0.82

MPC

0.030

ClinPred

0.24

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.043

gMVP

0.082

Mutation Taster

=88/12

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

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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