rs745985057

Variant names:

• chr14-104928922-C-T
• rs745985057
• NM_138790.5:c.458C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138790.5(PLD4):​c.458C>T​(p.Ser153Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00003 in 1,599,480 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: PLD4 NM_138790.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

Genes affected

PLD4 (HGNC:23792): (phospholipase D family member 4) Predicted to enable single-stranded DNA 5'-3' exodeoxyribonuclease activity. Predicted to be involved in hematopoietic progenitor cell differentiation; phagocytosis; and regulation of cytokine production involved in inflammatory response. Predicted to be located in early endosome and endoplasmic reticulum membrane. Predicted to be active in several cellular components, including endoplasmic reticulum; phagocytic vesicle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138790.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD4	NM_138790.5	MANE Select	c.458C>T	p.Ser153Phe	missense	Exon 4 of 11	NP_620145.2	Q96BZ4
	PLD4	NM_001308174.2		c.479C>T	p.Ser160Phe	missense	Exon 4 of 11	NP_001295103.1	F5H2B5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD4	ENST00000392593.9	TSL:1 MANE Select	c.458C>T	p.Ser153Phe	missense	Exon 4 of 11	ENSP00000376372.5	Q96BZ4
	PLD4	ENST00000540372.5	TSL:2	c.479C>T	p.Ser160Phe	missense	Exon 4 of 11	ENSP00000438677.1	F5H2B5
	PLD4	ENST00000862746.1		c.458C>T	p.Ser153Phe	missense	Exon 4 of 11	ENSP00000532805.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000204 AC: 5 AN: 245146 AF XY: 0.0000150

Gnomad AFR exome AF: 0.0000653

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000362

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000283 AC: 41 AN: 1447262 Hom.: 0 Cov.: 31 AF XY: 0.0000307 AC XY: 22 AN XY: 717112

African (AFR) AF: 0.0000301 AC: 1 AN: 33236

American (AMR) AF: 0.00 AC: 0 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39276

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52136

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5702

European-Non Finnish (NFE) AF: 0.0000345 AC: 38 AN: 1101350

Other (OTH) AF: 0.00 AC: 0 AN: 59674

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152218 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.47
MutPred		0.44		Gain of catalytic residue at D158 (P = 0.001)
MVP		0.42
MPC		0.42
ClinPred		0.92	D
GERP RS		3.2
Varity_R		0.48
gMVP		0.79
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745985057; hg19: chr14-105395259;