Variant 14-19428606-T-C 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.746A>G(p.Asn249Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000033 ( 0 hom., cov: 13)

Exomes 𝑓: 0.000050 ( 7 hom. )

Failed GnomAD Quality Control

Consequence

POTEG
NM_001005356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.323

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=0.13646105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTEG	NM_001005356.3 linkuse as main transcript	c.746A>G	p.Asn249Ser	missense_variant	3/11	ENST00000547848.5
POTEG	NR_027480.2 linkuse as main transcript	n.798A>G		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTEG	ENST00000547848.5 linkuse as main transcript	c.746A>G	p.Asn249Ser	missense_variant	3/11	1	NM_001005356.3	P1	Q6S5H5-3
POTEG	ENST00000622767.4 linkuse as main transcript	c.746A>G	p.Asn249Ser	missense_variant, NMD_transcript_variant	3/12	1			Q6S5H5-2
POTEG	ENST00000547722.1 linkuse as main transcript	c.746A>G	p.Asn249Ser	missense_variant, NMD_transcript_variant	3/12	2			Q6S5H5-4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

90946

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.0000671

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000496

AC:

AN:

1109496

Hom.:

Cov.:

AF XY:

0.0000559

AC XY:

AN XY:

554740

show subpopulations

Gnomad4 AFR exome

AF:

0.0000847

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000329

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000543

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000330

AC:

AN:

90994

Hom.:

Cov.:

AF XY:

0.0000229

AC XY:

AN XY:

43586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000671

Gnomad4 OTH

AF:

0.00

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

Nov 18, 2022

The c.746A>G (p.N249S) alteration is located in exon 3 (coding exon 3) of the POTEG gene. This alteration results from a A to G substitution at nucleotide position 746, causing the asparagine (N) at amino acid position 249 to be replaced by a serine (S). 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

0.089

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.51

M_CAP

Benign

0.0070

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.5

Sift

Benign

0.21

Sift4G

Benign

0.20

Vest4

0.072

MutPred

0.53

Gain of catalytic residue at I247 (P = 0.0171);

MVP

0.52

ClinPred

0.37

GERP RS

-0.75

Varity_R

0.033

gMVP

0.027

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