rs137875167

Variant names:

• chr22-31619756-G-A
• rs137875167
• NM_001326411.2:c.1086C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001326411.2(PISD):​c.1086C>T​(p.Gly362Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,614,170 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (3 hom.)
• Consequence: PISD NM_001326411.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.123
• Publications: 1 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), ClinGen, Ambry Genetics, G2P, Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.074).
• BP6: Variant 22-31619756-G-A is Benign according to our data. Variant chr22-31619756-G-A is described in ClinVar as Benign. ClinVar VariationId is 1600129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.123 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00157 (239/152356) while in subpopulation AFR AF = 0.00541 (225/41572). AF 95% confidence interval is 0.00483. There are 0 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PISD	NM_001326411.2	MANE Select	c.1086C>T	p.Gly362Gly	synonymous	Exon 8 of 8	NP_001313340.1	Q9UG56-3
	PISD	NM_001326412.1		c.1023C>T	p.Gly341Gly	synonymous	Exon 8 of 8	NP_001313341.1
	PISD	NM_001326413.2		c.1023C>T	p.Gly341Gly	synonymous	Exon 8 of 8	NP_001313342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PISD	ENST00000439502.7	TSL:1 MANE Select	c.1086C>T	p.Gly362Gly	synonymous	Exon 8 of 8	ENSP00000391739.2	Q9UG56-3
	PISD	ENST00000266095.9	TSL:1	c.984C>T	p.Gly328Gly	synonymous	Exon 9 of 9	ENSP00000266095.5	Q9UG56-2
	PISD	ENST00000460723.5	TSL:1	n.1269C>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 239 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000510 AC: 128 AN: 251078 AF XY: 0.000368

Gnomad AFR exome AF: 0.00603

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000222 AC: 325 AN: 1461814 Hom.: 3 Cov.: 32 AF XY: 0.000184 AC XY: 134 AN XY: 727218

African (AFR) AF: 0.00588 AC: 197 AN: 33478

American (AMR) AF: 0.000537 AC: 24 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111944

Other (OTH) AF: 0.000778 AC: 47 AN: 60396

GnomAD4 genome AF: 0.00157 AC: 239 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.00145 AC XY: 108 AN XY: 74502

African (AFR) AF: 0.00541 AC: 225 AN: 41572

American (AMR) AF: 0.000523 AC: 8 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000661 Hom.: 0

Bravo AF: 0.00200

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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: rs137875167; hg19: chr22-32015742; COSMIC: COSV56716682; COSMIC: COSV56716682;