22-31619176-C-T

Position:

• chr22-31619176-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326411.2(PISD):​c.*436G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 277,832 control chromosomes in the GnomAD database, including 8,751 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4575 hom., cov: 32)
  • Exomes 𝑓: 0.23 (4176 hom.)
• Consequence: PISD NM_001326411.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PISD	NM_001326411.2	c.*436G>A		3_prime_UTR_variant	8/8	ENST00000439502.7	NP_001313340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PISD	ENST00000439502.7	c.*436G>A		3_prime_UTR_variant	8/8	1	NM_001326411.2	ENSP00000391739.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36245 AN: 151818 Hom.: 4564 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.233 AC: 29356 AN: 125896 Hom.: 4176 Cov.: 0 AF XY: 0.248 AC XY: 17043 AN XY: 68646

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.239 AC: 36297 AN: 151936 Hom.: 4575 Cov.: 32 AF XY: 0.243 AC XY: 18070 AN XY: 74266

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.248

Alfa AF: 0.201 Hom.: 3847

Bravo AF: 0.243

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.4
DANN	Benign	0.85

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: rs8461; hg19: chr22-32015162;