Genetic Variant POTEJ:p.His736His (chr2-130656968-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.2208C>T(p.His736His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000506 in 1,592,804 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 27)

Exomes 𝑓: 0.00029 ( 14 hom. )

Consequence

POTEJ
NM_001277083.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.280

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=-0.62).

BP6

Variant 2-130656968-C-T is Benign according to our data. Variant chr2-130656968-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388206.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.28 with no splicing effect.

BS2

High AC in GnomAd4 at 387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POTEJ	NM_001277083.2 link	c.2208C>T	p.His736His	synonymous_variant	Exon 15 of 15	ENST00000409602.2	NP_001264012.1	P0CG39
POTEJ	XM_017004741.3 link	c.2238C>T	p.His746His	synonymous_variant	Exon 16 of 16		XP_016860230.1
POTEJ	XM_017004742.2 link	c.1119C>T	p.His373His	synonymous_variant	Exon 10 of 10		XP_016860231.1
POTEJ	XM_017004743.3 link	c.1065C>T	p.His355His	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.2208C>T	p.His736His	synonymous_variant	Exon 15 of 15	5	NM_001277083.2	ENSP00000387176.1		P0CG39

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

384

AN:

145532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000809

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:

0.0000603

Gnomad OTH

AF:

0.00254

GnomAD3 exomes

AF:

0.000902

AC:

AN:

77600

Hom.:

AF XY:

0.000806

AC XY:

AN XY:

38438

show subpopulations

Gnomad AFR exome

AF:

0.00989

Gnomad AMR exome

AF:

0.000538

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.000448

GnomAD4 exome

AF:

0.000290

AC:

419

AN:

1447168

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

193

AN XY:

720262

show subpopulations

Gnomad4 AFR exome

AF:

0.00924

Gnomad4 AMR exome

AF:

0.000584

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000373

Gnomad4 OTH exome

AF:

0.000568

GnomAD4 genome

AF:

0.00266

AC:

387

AN:

145636

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

190

AN XY:

71120

show subpopulations

Gnomad4 AFR

AF:

0.00977

Gnomad4 AMR

AF:

0.000808

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000603

Gnomad4 OTH

AF:

0.00251

Alfa

AF:

0.00167

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POTEJ: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.1

DANN

Benign

0.46

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