Genetic Variant PLPP6:p.Arg57Trp (chr9-4662544-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_203453.5(PLPP6):c.169C>T(p.Arg57Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,418,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PLPP6
NM_203453.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Publications

0 publications found

Variant links:

Genes affected

PLPP6 (HGNC:23682): (phospholipid phosphatase 6) Enables lipid phosphatase activity. Involved in phospholipid dephosphorylation. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLPP6 links:

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

SPATA6L links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3254362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203453.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPP6	NM_203453.5	MANE Select	c.169C>T	p.Arg57Trp	missense	Exon 1 of 1	NP_982278.3	Q8IY26
SPATA6L	NM_001353486.2	MANE Select	c.40-508G>A		intron	N/A	NP_001340415.1	Q8N4H0-1
SPATA6L	NM_001353484.2		c.40-508G>A		intron	N/A	NP_001340413.1	A0AA34QVF8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPP6	ENST00000381883.5	TSL:6 MANE Select	c.169C>T	p.Arg57Trp	missense	Exon 1 of 1	ENSP00000371307.2	Q8IY26
SPATA6L	ENST00000682582.1	MANE Select	c.40-508G>A		intron	N/A	ENSP00000506787.1	Q8N4H0-1
SPATA6L	ENST00000451763.6	TSL:1	n.189-508G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1418296

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

703870

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32578

American (AMR)

AF:

0.00

AC:

AN:

40392

Ashkenazi Jewish (ASJ)

AF:

0.0000410

AC:

AN:

24370

East Asian (EAS)

AF:

0.00

AC:

AN:

39084

South Asian (SAS)

AF:

0.00

AC:

AN:

82022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4218

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1099736

Other (OTH)

AF:

0.00

AC:

AN:

58750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

0.12

Eigen_PC

Benign

0.016

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

PhyloP100

2.5

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.35

MutPred

0.35

Loss of methylation at R57 (P = 0.0144)

MVP

0.32

MPC

1.2

ClinPred

0.95

GERP RS

3.1

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.23

gMVP

0.53

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over