chr1-242348152-C-T

Position:

• chr1-242348152-C-T

Variant summary

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

The NM_001372062.1(PLD5):​c.280G>A​(p.Glu94Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLD5 NM_001372062.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

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]

ACMG classification

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	c.280G>A	p.Glu94Lys	missense_variant	2/10	ENST00000536534.7	NP_001358991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD5	ENST00000536534.7	c.280G>A	p.Glu94Lys	missense_variant	2/10	1	NM_001372062.1	ENSP00000440896.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461628 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.280G>A (p.E94K) alteration is located in exon 3 (coding exon 2) of the PLD5 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the glutamic acid (E) at amino acid position 94 to be replaced by a lysine (K). 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	0.34
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	N;N;.;N
REVEL	Benign	0.23
Sift	Benign	0.039	D;D;.;T
Sift4G	Benign	0.11	T;T;T;.
Polyphen		1.0	D;D;D;.
Vest4		0.52
MutPred		0.47		Gain of ubiquitination at E94 (P = 0.0121);.;Gain of ubiquitination at E94 (P = 0.0121);.;
MVP		0.23
MPC		1.3
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-242511454;