11-479111-A-G

Position:

• chr11-479111-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030783.3(PTDSS2):​c.394A>G​(p.Ser132Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTDSS2 NM_030783.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTDSS2	NM_030783.3	c.394A>G	p.Ser132Gly	missense_variant	4/12	ENST00000308020.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTDSS2	ENST00000308020.6	c.394A>G	p.Ser132Gly	missense_variant	4/12	1	NM_030783.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2021

The c.394A>G (p.S132G) alteration is located in exon 4 (coding exon 4) of the PTDSS2 gene. This alteration results from a A to G substitution at nucleotide position 394, causing the serine (S) at amino acid position 132 to be replaced by a glycine (G). 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	Benign	0.21
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Benign	0.24	T
Sift4G	Benign	0.16	T
Polyphen		0.14	B
Vest4		0.60
MutPred		0.82		Loss of stability (P = 0.0811);
MVP		0.31
MPC		0.78
ClinPred		0.87	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-479111;