Genetic Variant ENTREP1:p.Thr148Lys (chr9-69336241-C-A) – 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_001347995.2(ENTREP1):c.443C>A(p.Thr148Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000377 in 1,589,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T148I) has been classified as Likely benign.

Frequency

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

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ENTREP1
NM_001347995.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.90

Publications

0 publications found

Variant links:

Genes affected

ENTREP1 (HGNC:24820): (endosomal transmembrane epsin interactor 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENTREP1 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=0.33446378).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTREP1	NM_001347995.2	MANE Select	c.443C>A	p.Thr148Lys	missense	Exon 2 of 11	NP_001334924.1	Q15884-4
ENTREP1	NM_001127608.3		c.-17C>A		5_prime_UTR	Exon 2 of 11	NP_001121080.1	Q15884-3
ENTREP1	NM_004816.5		c.-17C>A		5_prime_UTR	Exon 2 of 11	NP_004807.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTREP1	ENST00000303068.14	TSL:2 MANE Select	c.443C>A	p.Thr148Lys	missense	Exon 2 of 11	ENSP00000304435.8	Q15884-4
ENTREP1	ENST00000257515.12	TSL:1	c.-17C>A		5_prime_UTR	Exon 2 of 11	ENSP00000257515.8	Q15884-3
ENTREP1	ENST00000377216.4	TSL:1	n.-17C>A		non_coding_transcript_exon	Exon 2 of 10	ENSP00000366422.4	A0A0A0MRU1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152100

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

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1437876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716224

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32720

American (AMR)

AF:

0.0000232

AC:

AN:

43126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.00

AC:

AN:

39252

South Asian (SAS)

AF:

0.00

AC:

AN:

83832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00000365

AC:

AN:

1094704

Other (OTH)

AF:

0.00

AC:

AN:

59554

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000529729), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.295

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

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Benign

0.93

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.71

MetaRNN

Benign

0.33

PhyloP100

3.9

GERP RS

5.0

gMVP

0.73

Mutation Taster

=299/1

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

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