22-31619650-G-C

Variant names:

• chr22-31619650-G-C
• rs1663497424
• NM_001326411.2:c.1192C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001326411.2(PISD):​c.1192C>G​(p.Gln398Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PISD NM_001326411.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57
• 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), ClinGen, Ambry Genetics, G2P, Franklin by Genoox

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2876812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326411.2. 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
	PISD	NM_001326411.2	MANE Select	c.1192C>G	p.Gln398Glu	missense	Exon 8 of 8	NP_001313340.1	Q9UG56-3
	PISD	NM_001326412.1		c.1129C>G	p.Gln377Glu	missense	Exon 8 of 8	NP_001313341.1
	PISD	NM_001326413.2		c.1129C>G	p.Gln377Glu	missense	Exon 8 of 8	NP_001313342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PISD	ENST00000439502.7	TSL:1 MANE Select	c.1192C>G	p.Gln398Glu	missense	Exon 8 of 8	ENSP00000391739.2	Q9UG56-3
	PISD	ENST00000266095.9	TSL:1	c.1090C>G	p.Gln364Glu	missense	Exon 9 of 9	ENSP00000266095.5	Q9UG56-2
	PISD	ENST00000460723.5	TSL:1	n.1375C>G		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.30
Sift	Benign	0.095	T
Sift4G	Benign	0.11	T
Polyphen		0.36	B
Vest4		0.54
MutPred		0.44		Loss of MoRF binding (P = 0.0946)
MVP		0.17
MPC		0.68
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.42
gMVP		0.83
Mutation Taster		=35/65	disease causing

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

dbSNP: rs1663497424; hg19: chr22-32015636;