dbSNP rs955053105: PNMA8B:p.Glu519Lys (chr19-46493911-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020709.3(PNMA8B):c.1555G>A(p.Glu519Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,578,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 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: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

PNMA8B
NM_020709.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Publications

3 publications found

Variant links:

Genes affected

PNMA8B (HGNC:29206): (PNMA family member 8B)

PNMA8B links:

ENSG00000291145 (HGNC:):

ENSG00000291145 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09994912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMA8B	NM_020709.3	MANE Select	c.1555G>A	p.Glu519Lys	missense	Exon 1 of 1	NP_065760.1	Q9ULN7-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNMA8B	ENST00000599531.2	TSL:6 MANE Select	c.1555G>A	p.Glu519Lys	missense	Exon 1 of 1	ENSP00000473036.1	Q9ULN7-5
PNMA8B	ENST00000594749.1	TSL:5	n.165+1804G>A		intron	N/A
ENSG00000291145	ENST00000602017.8	TSL:3	n.425-12471G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

224526

AF XY:

0.00000811

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000358

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1425944

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31436

American (AMR)

AF:

0.0000535

AC:

AN:

37382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24336

East Asian (EAS)

AF:

0.00

AC:

AN:

39138

South Asian (SAS)

AF:

0.00

AC:

AN:

84226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50898

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1094488

Other (OTH)

AF:

0.00

AC:

AN:

58476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000369

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.97

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.56

M_CAP

Benign

0.077

MetaRNN

Benign

0.10

PhyloP100

1.0

PrimateAI

Benign

0.46

Sift4G

Benign

0.20

Polyphen

0.87

Vest4

0.13

MVP

0.14

GERP RS

0.91

Varity_R

0.028

gMVP

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over