PDSS2 p.Phe3Leu

Variant names:

• chr6-107459277-A-T
• NM_020381.4:c.9T>A
• PDSS2 p.Phe3Leu

Your query was ambiguous. Multiple possible variants found:

• chr6-107459277-A-T
• chr6-107459277-A-C
• chr6-107459279-A-G
• chr6-107459277-AAA-GAG
• chr6-107459277-AAA-TAG
• chr6-107459277-AAA-CAG

Variant summary

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

The NM_020381.4(PDSS2):​c.9T>A​(p.Phe3Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDSS2 NM_020381.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.752
• Publications: 0 publications found

Genes affected

PDSS2 (HGNC:23041): (decaprenyl diphosphate synthase subunit 2) The protein encoded by this gene is an enzyme that synthesizes the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. Defects in this gene are a cause of coenzyme Q10 deficiency.[provided by RefSeq, Oct 2009]

PDSS2 Gene-Disease associations (from GenCC):

• coenzyme Q10 deficiency, primary, 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with nephrotic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047819912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020381.4. 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
	PDSS2	NM_020381.4	MANE Select	c.9T>A	p.Phe3Leu	missense	Exon 1 of 8	NP_065114.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDSS2	ENST00000369037.9	TSL:1 MANE Select	c.9T>A	p.Phe3Leu	missense	Exon 1 of 8	ENSP00000358033.4	Q86YH6-1
	PDSS2	ENST00000369031.4	TSL:1	c.9T>A	p.Phe3Leu	missense	Exon 1 of 4	ENSP00000358027.4	Q86YH6-2
	PDSS2	ENST00000900080.1		c.9T>A	p.Phe3Leu	missense	Exon 1 of 9	ENSP00000570139.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.75
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
PromoterAI		-0.070	Neutral
Varity_R		0.053
gMVP		0.40
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-107780481;