Variant 1-242524140-T-G 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.137A>C(p.Gln46Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000208 in 1,535,518 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

PLD5
NM_001372062.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22252434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLD5	NM_001372062.1 linkuse as main transcript	c.137A>C	p.Gln46Pro	missense_variant	1/10	ENST00000536534.7
PLD5	NM_001320272.2 linkuse as main transcript	c.-147A>C		5_prime_UTR_variant	2/11
PLD5	XM_011544115.3 linkuse as main transcript	c.-85+3441A>C		intron_variant
PLD5	XM_011544116.3 linkuse as main transcript	c.-85+3441A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD5	ENST00000536534.7 linkuse as main transcript	c.137A>C	p.Gln46Pro	missense_variant	1/10	1	NM_001372062.1	P1	Q8N7P1-1
PLD5	ENST00000442594.6 linkuse as main transcript	c.137A>C	p.Gln46Pro	missense_variant	2/11	5		P1	Q8N7P1-1
PLD5	ENST00000467561.5 linkuse as main transcript	c.137A>C	p.Gln46Pro	missense_variant, NMD_transcript_variant	1/6	5
PLD5	ENST00000366545.5 linkuse as main transcript	c.137A>C	p.Gln46Pro	missense_variant, NMD_transcript_variant	2/11	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000194

AC:

AN:

134198

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

73054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00106

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:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1383338

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

682630

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000813

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:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

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

Feb 27, 2024

The c.137A>C (p.Q46P) alteration is located in exon 2 (coding exon 1) of the PLD5 gene. This alteration results from a A to C substitution at nucleotide position 137, causing the glutamine (Q) at amino acid position 46 to be replaced by a proline (P). 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

Benign

0.33

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.10

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.015

T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.060

N;.

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.11

T;T

Polyphen

0.93

P;P

Vest4

0.49

MutPred

0.25

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);

MVP

0.14

MPC

0.91

ClinPred

0.22

GERP RS

3.7

Varity_R

0.20

gMVP

0.80

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