Genetic Variant PISD:c.*436G>A (chr22-31619176-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

14 publications found

Variant links:

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), ClinGen, Ambry Genetics, G2P, Franklin by Genoox

PISD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326411.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PISD	NM_001326411.2	MANE Select	c.*436G>A	3_prime_UTR	Exon 8 of 8	NP_001313340.1	Q9UG56-3
PISD	NM_001326412.1		c.*436G>A	3_prime_UTR	Exon 8 of 8	NP_001313341.1
PISD	NM_001326413.2		c.*436G>A	3_prime_UTR	Exon 8 of 8	NP_001313342.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PISD	ENST00000439502.7	TSL:1 MANE Select	c.*436G>A	3_prime_UTR	Exon 8 of 8	ENSP00000391739.2	Q9UG56-3
PISD	ENST00000266095.9	TSL:1	c.*436G>A	3_prime_UTR	Exon 9 of 9	ENSP00000266095.5	Q9UG56-2
PISD	ENST00000460723.5	TSL:1	n.1849G>A	non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36245

AN:

151818

Hom.:

4564

Cov.:

show subpopulations

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.:

AF XY:

0.248

AC XY:

17043

AN XY:

68646

show subpopulations

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:

AN:

438

European-Non Finnish (NFE)

AF:

0.186

AC:

13546

AN:

72686

Other (OTH)

AF:

0.208

AC:

1251

AN:

6012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

985

1969

2954

3938

4923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.239

AC:

36297

AN:

151936

Hom.:

4575

Cov.:

AF XY:

0.243

AC XY:

18070

AN XY:

74266

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.197

AC:

13358

AN:

67970

Other (OTH)

AF:

0.248

AC:

520

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1330

2660

3990

5320

6650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.4

(source)

DANN

Benign

0.85

PhyloP100

0.015

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over