NM_001326411.2:c.1157C>A

Variant names:

• chr22-31619685-G-T
• rs368767591
• NM_001326411.2:c.1157C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001326411.2(PISD):​c.1157C>A​(p.Ala386Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PISD NM_001326411.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PISD	NM_001326411.2	c.1157C>A	p.Ala386Asp	missense_variant	Exon 8 of 8	ENST00000439502.7	NP_001313340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PISD	ENST00000439502.7	c.1157C>A	p.Ala386Asp	missense_variant	Exon 8 of 8	1	NM_001326411.2	ENSP00000391739.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;.;D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	.;D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.9	.;.;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.2	D;D;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.75
MutPred		0.45		.;.;Gain of solvent accessibility (P = 0.0596);
MVP		0.41
MPC		1.3
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.83
gMVP		0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs368767591; hg19: chr22-32015671;