chr22-31625772-G-C

Variant names:

• chr22-31625772-G-C
• rs199973333
• ENST00000266095.9:c.44C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000266095.9(PISD):​c.44C>G​(p.Ala15Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A15V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PISD ENST00000266095.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• Publications: 0 publications found

Genes affected

PISD (HGNC:8999): (phosphatidylserine decarboxylase) The protein encoded by this gene catalyzes the conversion of phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane. The encoded protein is active in phospholipid metabolism and interorganelle trafficking of phosphatidylserine. [provided by RefSeq, May 2016]

PISD Gene-Disease associations (from GenCC):

• Liberfarb syndrome

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Franklin by Genoox, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16011295).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000266095.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PISD	NM_001326411.2	MANE Select	c.322-3887C>G		intron	N/A	NP_001313340.1
	PISD	NM_001326415.2		c.44C>G	p.Ala15Gly	missense	Exon 3 of 9	NP_001313344.1
	PISD	NM_001326416.2		c.44C>G	p.Ala15Gly	missense	Exon 5 of 11	NP_001313345.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PISD	ENST00000266095.9	TSL:1	c.44C>G	p.Ala15Gly	missense	Exon 3 of 9	ENSP00000266095.5
	PISD	ENST00000439502.7	TSL:1 MANE Select	c.322-3887C>G		intron	N/A	ENSP00000391739.2
	PISD	ENST00000460723.5	TSL:1	n.329-3887C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.036
Sift	Uncertain	0.018	D
Sift4G	Benign	0.22	T
Polyphen		0.065	B
Vest4		0.19
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.043
MPC		0.33
ClinPred		0.58	D
GERP RS		3.9
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs199973333; hg19: chr22-32021758;