dbSNP rs1182361420: POTED:p.Gly39Ser (chr21-13610343-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_174981.6(POTED):c.115G>A(p.Gly39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000082 ( 1 hom., cov: 4)

Exomes 𝑓: 0.0000053 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

POTED
NM_174981.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

Publications

0 publications found

Variant links:

Genes affected

POTED (HGNC:23822): (POTE ankyrin domain family member D) Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

POTED links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048320055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POTED	NM_174981.6 link	c.115G>A	p.Gly39Ser	missense_variant	Exon 1 of 11	ENST00000299443.6	NP_778146.2	Q86YR6
POTED	XM_006723997.4 link	c.115G>A	p.Gly39Ser	missense_variant	Exon 1 of 8		XP_006724060.1
POTED	XM_011529550.3 link	c.115G>A	p.Gly39Ser	missense_variant	Exon 1 of 7		XP_011527852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POTED	ENST00000299443.6 link	c.115G>A	p.Gly39Ser	missense_variant	Exon 1 of 11	1	NM_174981.6	ENSP00000299443.5		Q86YR6
POTED	ENST00000620442.4 link	c.115G>A	p.Gly39Ser	missense_variant	Exon 1 of 8	1		ENSP00000484512.1		A0A087X1W7

Frequencies

GnomAD3 genomes

AF:

0.0000818

AC:

AN:

36660

Hom.:

Cov.:

show subpopulations

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000523

AC:

AN:

38256

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000531

AC:

AN:

565382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

288456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5150

American (AMR)

AF:

0.00

AC:

AN:

20982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10338

East Asian (EAS)

AF:

0.00

AC:

AN:

10318

South Asian (SAS)

AF:

0.00

AC:

AN:

42600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1296

European-Non Finnish (NFE)

AF:

0.00000714

AC:

AN:

420216

Other (OTH)

AF:

0.00

AC:

AN:

24418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000818

AC:

AN:

36660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

16830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3336

American (AMR)

AF:

0.00

AC:

AN:

4406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

870

East Asian (EAS)

AF:

0.00

AC:

AN:

550

South Asian (SAS)

AF:

0.00

AC:

AN:

1220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

22706

Other (OTH)

AF:

0.00

AC:

AN:

440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.115G>A (p.G39S) alteration is located in exon 1 (coding exon 1) of the POTED gene. This alteration results from a G to A substitution at nucleotide position 115, causing the glycine (G) at amino acid position 39 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

0.095

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

PhyloP100

0.15

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.98

.;N

REVEL

Benign

0.016

Sift

Uncertain

0.0040

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.088

.;B

Vest4

0.077

MutPred

0.17

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);

MVP

0.082

ClinPred

0.14

PromoterAI

-0.0092

Neutral

(source)

Varity_R

0.13

gMVP

0.0050

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over