chr22-31619176-C-T

Variant names:

• chr22-31619176-C-T
• rs8461
• ENST00000460723.5:n.1849G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460723.5(PISD):​n.1849G>A variant causes a non coding transcript exon 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 ENST00000460723.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 14 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), Ambry Genetics, Franklin by Genoox, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PISD	NM_001326411.2	c.*436G>A		3_prime_UTR_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.*436G>A		3_prime_UTR_variant	Exon 8 of 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

African (AFR) AF: 0.289 AC: 857 AN: 2970

American (AMR) AF: 0.269 AC: 1310 AN: 4862

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 450 AN: 2778

East Asian (EAS) AF: 0.420 AC: 1864 AN: 4438

South Asian (SAS) AF: 0.349 AC: 8874 AN: 25440

European-Finnish (FIN) AF: 0.176 AC: 1107 AN: 6272

Middle Eastern (MID) AF: 0.221 AC: 97 AN: 438

European-Non Finnish (NFE) AF: 0.186 AC: 13546 AN: 72686

Other (OTH) AF: 0.208 AC: 1251 AN: 6012

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

African (AFR) AF: 0.286 AC: 11827 AN: 41370

American (AMR) AF: 0.261 AC: 3980 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2137 AN: 5156

South Asian (SAS) AF: 0.374 AC: 1801 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1897 AN: 10576

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13358 AN: 67970

Other (OTH) AF: 0.248 AC: 520 AN: 2100

Alfa AF: 0.211 Hom.: 8023

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
PhyloP100		0.015
Mutation Taster		=99/1	polymorphism (auto)

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: rs8461; hg19: chr22-32015162;