Variant 14-19416319-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005356.3(POTEG):c.1166G>C(p.Arg389Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000873 in 145,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00054 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POTEG
NM_001005356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

POTEG (HGNC:33896): (POTE ankyrin domain family member G)

POTEG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09067634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTEG	NM_001005356.3 linkuse as main transcript	c.1166G>C	p.Arg389Thr	missense_variant	7/11	ENST00000547848.5
POTEG	NR_027480.2 linkuse as main transcript	n.1218G>C		non_coding_transcript_exon_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTEG	ENST00000547848.5 linkuse as main transcript	c.1166G>C	p.Arg389Thr	missense_variant	7/11	1	NM_001005356.3	P1	Q6S5H5-3
POTEG	ENST00000622767.4 linkuse as main transcript	c.1166G>C	p.Arg389Thr	missense_variant, NMD_transcript_variant	7/12	1			Q6S5H5-2
POTEG	ENST00000547722.1 linkuse as main transcript	c.*453G>C		3_prime_UTR_variant, NMD_transcript_variant	8/12	2			Q6S5H5-4

Frequencies

GnomAD3 genomes

AF:

0.000873

AC:

127

AN:

145500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00162

Gnomad SAS

AF:

0.00271

Gnomad FIN

AF:

0.00153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000963

Gnomad OTH

AF:

0.000499

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000545

AC:

762

AN:

1399408

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

388

AN XY:

695714

show subpopulations

Gnomad4 AFR exome

AF:

0.000133

Gnomad4 AMR exome

AF:

0.000349

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000131

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.000984

Gnomad4 NFE exome

AF:

0.000510

Gnomad4 OTH exome

AF:

0.000572

GnomAD4 genome

AF:

0.000873

AC:

127

AN:

145508

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

AN XY:

70656

show subpopulations

Gnomad4 AFR

AF:

0.000278

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00163

Gnomad4 SAS

AF:

0.00272

Gnomad4 FIN

AF:

0.00153

Gnomad4 NFE

AF:

0.000963

Gnomad4 OTH

AF:

0.000497

Alfa

AF:

0.00101

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.1166G>C (p.R389T) alteration is located in exon 7 (coding exon 7) of the POTEG gene. This alteration results from a G to C substitution at nucleotide position 1166, causing the arginine (R) at amino acid position 389 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.65

M_CAP

Benign

0.0013

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.4

Sift

Uncertain

0.016

Sift4G

Benign

0.091

Vest4

0.47

MutPred

0.23

Gain of phosphorylation at R389 (P = 0.0216);

MVP

0.12

ClinPred

0.25

GERP RS

-0.90

Varity_R

0.049

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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