chr22-31619745-C-A

Variant names:

• chr22-31619745-C-A
• rs567105342
• NM_001326411.2:c.1097G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001326411.2(PISD):​c.1097G>T​(p.Arg366Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PISD NM_001326411.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30699214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PISD	NM_001326411.2	c.1097G>T	p.Arg366Leu	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.1097G>T	p.Arg366Leu	missense_variant	Exon 8 of 8	1	NM_001326411.2	ENSP00000391739.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;.;T
Eigen	Benign	0.012
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.30	T;T;D
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.53
MutPred		0.52		.;.;Loss of ubiquitination at K367 (P = 0.0435);
MVP		0.082
MPC		0.51
ClinPred		0.73	D
GERP RS		3.1
Varity_R		0.18
gMVP		0.70

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: rs567105342; hg19: chr22-32015731;