Variant 11-450471-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000308020.6(PTDSS2):c.16C>T(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,231,114 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 26 hom. )

Consequence

PTDSS2
ENST00000308020.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.409

Variant links:

Genes affected

PTDSS2 (HGNC:15463): (phosphatidylserine synthase 2) The protein encoded by this gene catalyzes the conversion of phosphatidylethanolamine to phosphatidylserine, a structural membrane phospholipid that functions in cell signaling, blood coagulation, and apoptosis. The encoded enzyme also has a high affinity for docosahexaenoic acid (DHA) and can use it to make DHA-containing phosphatidylserine. [provided by RefSeq, Jul 2016]

PTDSS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00677076).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTDSS2	NM_030783.3 linkuse as main transcript	c.16C>T	p.Arg6Cys	missense_variant	1/12	ENST00000308020.6	NP_110410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTDSS2	ENST00000308020.6 linkuse as main transcript	c.16C>T	p.Arg6Cys	missense_variant	1/12	1	NM_030783.3	ENSP00000308258	P1

Frequencies

GnomAD3 genomes

AF:

0.00469

AC:

713

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00964

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00730

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00482

AC:

AN:

3530

Hom.:

AF XY:

0.00224

AC XY:

AN XY:

1784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00501

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00583

AC:

6292

AN:

1078920

Hom.:

Cov.:

AF XY:

0.00574

AC XY:

2924

AN XY:

509526

show subpopulations

Gnomad4 AFR exome

AF:

0.000974

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00407

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000514

Gnomad4 FIN exome

AF:

0.00944

Gnomad4 NFE exome

AF:

0.00630

Gnomad4 OTH exome

AF:

0.00410

GnomAD4 genome

AF:

0.00468

AC:

713

AN:

152194

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00964

Gnomad4 NFE

AF:

0.00730

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.00362

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00493

AC:

ExAC

AF:

0.000255

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 29, 2023

The c.16C>T (p.R6C) alteration is located in exon 1 (coding exon 1) of the PTDSS2 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the arginine (R) at amino acid position 6 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.78

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Benign

0.089

Sift

Benign

0.040

Sift4G

Uncertain

0.040

Polyphen

0.0060

Vest4

0.15

MVP

0.34

MPC

0.98

ClinPred

0.19

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over