Variant 1-242524137-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001372062.1(PLD5):c.140A>G(p.Gln47Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000488 in 1,535,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

PLD5
NM_001372062.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06952128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD5	NM_001372062.1 link	c.140A>G	p.Gln47Arg	missense_variant	1/10	ENST00000536534.7	NP_001358991.1
PLD5	NM_001320272.2 link	c.-144A>G		5_prime_UTR_variant	2/11		NP_001307201.1	Q8N7P1-2A0A024R3S7
PLD5	XM_011544115.3 link	c.-85+3444A>G		intron_variant			XP_011542417.1	Q8N7P1
PLD5	XM_011544116.3 link	c.-85+3444A>G		intron_variant			XP_011542418.1	Q8N7P1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLD5	ENST00000536534.7 link	c.140A>G	p.Gln47Arg	missense_variant	1/10	1	NM_001372062.1	ENSP00000440896.1	Q8N7P1-1
PLD5	ENST00000442594.6 link	c.140A>G	p.Gln47Arg	missense_variant	2/11	5		ENSP00000414188.3	Q8N7P1-1
PLD5	ENST00000366545.5 link	n.140A>G		non_coding_transcript_exon_variant	2/11	2		ENSP00000355503.4	J3KP61
PLD5	ENST00000467561.5 link	n.140A>G		non_coding_transcript_exon_variant	1/6	5		ENSP00000440132.1	F5GXZ8

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

134130

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

73012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000900

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:

0.00

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.0000195

AC:

AN:

1383336

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

682626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000701

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.000315

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000291

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

Jun 25, 2024

The c.140A>G (p.Q47R) alteration is located in exon 2 (coding exon 1) of the PLD5 gene. This alteration results from a A to G substitution at nucleotide position 140, causing the glutamine (Q) at amino acid position 47 to be replaced by an arginine (R). 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

0.49

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.70

.;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.0

L;L

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.74

N;.

REVEL

Benign

0.18

Sift

Uncertain

0.023

D;.

Sift4G

Benign

0.12

T;T

Polyphen

0.85

P;P

Vest4

0.34

MutPred

0.28

Loss of catalytic residue at Q47 (P = 0.0194);Loss of catalytic residue at Q47 (P = 0.0194);

MVP

0.23

MPC

0.58

ClinPred

0.14

GERP RS

3.7

Varity_R

0.15

gMVP

0.70

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