Variant chr14-18967817-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145442.1(POTEM):c.332G>A(p.Gly111Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000956 in 104,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000096 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POTEM
NM_001145442.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

POTEM (HGNC:37096): (POTE ankyrin domain family member M) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

POTEM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14505005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTEM	NM_001145442.1 linkuse as main transcript	c.332G>A	p.Gly111Glu	missense_variant	1/11	ENST00000547889.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
POTEM	ENST00000547889.6 linkuse as main transcript	c.332G>A	p.Gly111Glu	missense_variant	1/11	1	NM_001145442.1	P1
POTEM	ENST00000616847.1 linkuse as main transcript	c.332G>A	p.Gly111Glu	missense_variant, NMD_transcript_variant	1/12	1
POTEM	ENST00000552966.5 linkuse as main transcript	c.332G>A	p.Gly111Glu	missense_variant, NMD_transcript_variant	1/12	2

Frequencies

GnomAD3 genomes

AF:

0.00000956

AC:

AN:

104572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000421

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000281

AC:

AN:

1421360

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708456

show subpopulations

Gnomad4 AFR exome

AF:

0.0000620

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000956

AC:

AN:

104572

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

50754

show subpopulations

Gnomad4 AFR

AF:

0.0000421

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Oct 10, 2023

The c.332G>A (p.G111E) alteration is located in exon 1 (coding exon 1) of the POTEM gene. This alteration results from a G to A substitution at nucleotide position 332, causing the glycine (G) at amino acid position 111 to be replaced by a glutamic acid (E). 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

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.014

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.76

M_CAP

Benign

0.0039

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.046

Vest4

0.28

MutPred

0.44

Gain of catalytic residue at K116 (P = 0);

MVP

0.061

ClinPred

0.22

GERP RS

0.57

Varity_R

0.12

gMVP

0.030

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