15-42070015-G-T

Variant names:

• chr15-42070015-G-T
• NM_178034.4:c.2124C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_178034.4(PLA2G4D):​c.2124C>A​(p.His708Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLA2G4D NM_178034.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.502
• Publications: 0 publications found

Genes affected

PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03720182).
• BP6: Variant 15-42070015-G-T is Benign according to our data. Variant chr15-42070015-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3889765.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178034.4. 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
	PLA2G4D	NM_178034.4	MANE Select	c.2124C>A	p.His708Gln	missense	Exon 19 of 20	NP_828848.3	Q86XP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4D	ENST00000290472.4	TSL:1 MANE Select	c.2124C>A	p.His708Gln	missense	Exon 19 of 20	ENSP00000290472.3	Q86XP0-1
	PLA2G4D	ENST00000560932.1	TSL:1	n.1277C>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1359218 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 669614

African (AFR) AF: 0.00 AC: 0 AN: 28388

American (AMR) AF: 0.00 AC: 0 AN: 28484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23956

East Asian (EAS) AF: 0.00 AC: 0 AN: 31644

South Asian (SAS) AF: 0.00 AC: 0 AN: 72946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063282

Other (OTH) AF: 0.00 AC: 0 AN: 56350

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.073
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.23
DEOGEN2	Benign	0.00065	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.031	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.50
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.023
Sift	Benign	0.53	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.25		Loss of glycosylation at S703 (P = 0.1436)
MVP		0.10
MPC		0.053
ClinPred		0.052	T
GERP RS		-3.5
Varity_R		0.14
gMVP		0.10

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

Other links and lift over

hg19: chr15-42362213;