Variant 1-242524204-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001372062.1(PLD5):c.73C>T(p.Arg25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,533,546 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: 𝑓 0.00011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PLD5
NM_001372062.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

PLD5 (HGNC:26879): (phospholipase D family member 5) Predicted to enable catalytic activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3904506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLD5	NM_001372062.1 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/10	ENST00000536534.7
PLD5	NM_001320272.2 linkuse as main transcript	c.-211C>T		5_prime_UTR_variant	2/11
PLD5	XM_011544115.3 linkuse as main transcript	c.-85+3377C>T		intron_variant
PLD5	XM_011544116.3 linkuse as main transcript	c.-85+3377C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD5	ENST00000536534.7 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/10	1	NM_001372062.1	P1	Q8N7P1-1
PLD5	ENST00000442594.6 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	2/11	5		P1	Q8N7P1-1
PLD5	ENST00000467561.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant, NMD_transcript_variant	1/6	5
PLD5	ENST00000366545.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant, NMD_transcript_variant	2/11	2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000114

AC:

AN:

131920

Hom.:

AF XY:

0.0000974

AC XY:

AN XY:

71874

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000199

AC:

275

AN:

1381536

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

116

AN XY:

681710

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

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:

0.0000295

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000105

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000945

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

Aug 16, 2021

The c.73C>T (p.R25C) alteration is located in exon 2 (coding exon 1) of the PLD5 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the arginine (R) at amino acid position 25 to be replaced by a cysteine (C). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.021

T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.81

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

0.95

D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.89

N;.

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.48

MutPred

0.25

Loss of MoRF binding (P = 0.0156);Loss of MoRF binding (P = 0.0156);

MVP

0.23

MPC

1.4

ClinPred

0.27

GERP RS

3.5

Varity_R

0.25

gMVP

0.37

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