Genetic Variant POTEJ:p.Asn675Asn (chr2-130656785-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001277083.2(POTEJ):c.2025C>T(p.Asn675Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 149,676 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 37)

Exomes 𝑓: 0.000082 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

POTEJ
NM_001277083.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.230

Variant links:

Genes affected

POTEJ (HGNC:37094): (POTE ankyrin domain family member J) Involved in retina homeostasis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

POTEJ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-130656785-C-T is Benign according to our data. Variant chr2-130656785-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3778111.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.23 with no splicing effect.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POTEJ	NM_001277083.2 link	c.2025C>T	p.Asn675Asn	synonymous_variant	Exon 15 of 15	ENST00000409602.2	NP_001264012.1	P0CG39
POTEJ	XM_017004741.3 link	c.2055C>T	p.Asn685Asn	synonymous_variant	Exon 16 of 16		XP_016860230.1
POTEJ	XM_017004742.2 link	c.936C>T	p.Asn312Asn	synonymous_variant	Exon 10 of 10		XP_016860231.1
POTEJ	XM_017004743.3 link	c.882C>T	p.Asn294Asn	synonymous_variant	Exon 8 of 8		XP_016860232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POTEJ	ENST00000409602.2 link	c.2025C>T	p.Asn675Asn	synonymous_variant	Exon 15 of 15	5	NM_001277083.2	ENSP00000387176.1		P0CG39

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

149570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000397

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.000971

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000815

AC:

119

AN:

1459796

Hom.:

Cov.:

177

AF XY:

0.0000675

AC XY:

AN XY:

726204

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000792

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000107

AC:

AN:

149676

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73198

show subpopulations

Gnomad4 AFR

AF:

0.0000507

Gnomad4 AMR

AF:

0.000397

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POTEJ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.2

DANN

Benign

0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over