Genetic Variant POTEI:p.Val14Val (chr2-130509194-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_001277406.2(POTEI):c.42G>A(p.Val14Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,409,286 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000079 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

POTEI
NM_001277406.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.914

Variant links:

Genes affected

POTEI (HGNC:37093): (POTE ankyrin domain family member I) Involved in retina homeostasis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

POTEI 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=-0.95).

BP6

Variant 2-130509194-C-T is Benign according to our data. Variant chr2-130509194-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651369.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.914 with no splicing effect.

BS2

High AC in GnomAdExome4 at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POTEI	NM_001277406.2 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 1 of 15	ENST00000451531.7	NP_001264335.1	P0CG38
POTEI	NM_001371926.1 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 2 of 17		NP_001358855.1
POTEI	XM_017004732.3 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 2 of 16		XP_016860221.1
POTEI	XM_024453046.2 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 2 of 16		XP_024308814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POTEI	ENST00000451531.7 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 1 of 15	1	NM_001277406.2	ENSP00000392718.2	P0CG38
POTEI	ENST00000631234.1 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 1 of 13	2		ENSP00000486532.1	A0A0D9SFE8
POTEI	ENST00000652235.1 link	c.42G>A	p.Val14Val	synonymous_variant	Exon 2 of 4			ENSP00000499032.1	A0A494C1H2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

77976

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00330

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000534

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

224350

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

122404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00310

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000403

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000788

AC:

111

AN:

1409286

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

701950

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00319

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000115

AC:

AN:

77976

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

36590

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00330

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000534

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000336

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POTEI: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.8

DANN

Benign

0.42

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

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