Variant 1-242524221-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001372062.1(PLD5):c.56A>C(p.Gln19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 1,531,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

PLD5
NM_001372062.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD5	NM_001372062.1 linkuse as main transcript	c.56A>C	p.Gln19Pro	missense_variant	1/10	ENST00000536534.7	NP_001358991.1
PLD5	NM_001320272.2 linkuse as main transcript	c.-228A>C		5_prime_UTR_variant	2/11		NP_001307201.1	Q8N7P1-2A0A024R3S7
PLD5	XM_011544115.3 linkuse as main transcript	c.-85+3360A>C		intron_variant			XP_011542417.1	Q8N7P1
PLD5	XM_011544116.3 linkuse as main transcript	c.-85+3360A>C		intron_variant			XP_011542418.1	Q8N7P1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLD5	ENST00000536534.7 linkuse as main transcript	c.56A>C	p.Gln19Pro	missense_variant	1/10	1	NM_001372062.1	ENSP00000440896.1	Q8N7P1-1
PLD5	ENST00000442594.6 linkuse as main transcript	c.56A>C	p.Gln19Pro	missense_variant	2/11	5		ENSP00000414188.3	Q8N7P1-1
PLD5	ENST00000366545.5 linkuse as main transcript	n.56A>C		non_coding_transcript_exon_variant	2/11	2		ENSP00000355503.4	J3KP61
PLD5	ENST00000467561.5 linkuse as main transcript	n.56A>C		non_coding_transcript_exon_variant	1/6	5		ENSP00000440132.1	F5GXZ8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000311

AC:

AN:

128436

Hom.:

AF XY:

0.0000143

AC XY:

AN XY:

70136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000167

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:

0.00000290

AC:

AN:

1379668

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680810

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000113

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:

0.0000132

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.0000264

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 03, 2024

The c.56A>C (p.Q19P) 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 56, causing the glutamine (Q) at amino acid position 19 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.55

.;T

M_CAP

Pathogenic

0.69

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.85

N;.

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.82

P;P

Vest4

0.60

MutPred

0.15

Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);

MVP

0.18

MPC

0.64

ClinPred

0.33

GERP RS

3.5

Varity_R

0.48

gMVP

0.47

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