Genetic Variant PNMA8B:p.Arg569Leu (chr19-46493760-C-A) – 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.1706G>T(p.Arg569Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,352,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R569W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000086 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

PNMA8B
NM_020709.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.179

Publications

0 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=0.11591199).

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.1706G>T	p.Arg569Leu	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.1706G>T	p.Arg569Leu	missense	Exon 1 of 1	ENSP00000473036.1	Q9ULN7-5
PNMA8B	ENST00000594749.1	TSL:5	n.165+1955G>T		intron	N/A
ENSG00000291145	ENST00000602017.8	TSL:3	n.425-12320G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000864

AC:

AN:

115784

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:

0.0000208

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

24540

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000461

AC:

AN:

1236448

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

602562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24116

American (AMR)

AF:

0.00

AC:

AN:

12236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18326

East Asian (EAS)

AF:

0.00

AC:

AN:

28752

South Asian (SAS)

AF:

0.00

AC:

AN:

56158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4028

European-Non Finnish (NFE)

AF:

0.0000554

AC:

AN:

1010480

Other (OTH)

AF:

0.0000196

AC:

AN:

50902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.549

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:

0.00000864

AC:

AN:

115784

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

57106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33072

American (AMR)

AF:

0.00

AC:

AN:

11760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2672

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

48006

Other (OTH)

AF:

0.00

AC:

AN:

1542

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

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000116

AC:

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

0.34

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.95

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.41

M_CAP

Benign

0.022

MetaRNN

Benign

0.12

PhyloP100

-0.18

PrimateAI

Uncertain

0.76

Sift4G

Pathogenic

0.0

Vest4

0.15

MVP

0.45

GERP RS

-1.2

Varity_R

0.068

gMVP

0.11

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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