rs199973333

chr22-31625772-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000266095.9(PISD):c.44C>T(p.Ala15Val) variant causes a missense change. The variant allele was found at a frequency of 0.000124 in 1,592,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A15A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PISD ENST00000266095.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026309818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PISD	NM_001326411.2	c.322-3887C>T		intron_variant		ENST00000439502.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PISD	ENST00000439502.7	c.322-3887C>T		intron_variant		1	NM_001326411.2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000222 AC: 47 AN: 212132 Hom.: 0 AF XY: 0.000253 AC XY: 29 AN XY: 114616

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000610

Gnomad SAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000648

Gnomad OTH exome AF: 0.000935

GnomAD4 exome AF: 0.000117 AC: 168 AN: 1439864 Hom.: 0 Cov.: 31 AF XY: 0.000125 AC XY: 89 AN XY: 714166

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.000931

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.000302

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.0000763

Gnomad4 OTH exome AF: 0.000286

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74480

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000168 Hom.: 0

Bravo AF: 0.000208

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000998 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	18
Dann	Uncertain	0.98
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.66	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.026	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.070	N;N;N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.11	T;T;T;T;T;T;T
Sift4G	Benign	0.26	T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;.;.;.
Vest4		0.23
MVP		0.043
MPC		0.30
ClinPred		0.029	T
GERP RS		3.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199973333; hg19: chr22-32021758;