8-96262138-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_014754.3(PTDSS1):c.98C>G(p.Thr33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PTDSS1 NM_014754.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.51

Genes affected

PTDSS1 (HGNC:9587): (phosphatidylserine synthase 1) The protein encoded by this gene catalyzes the formation of phosphatidylserine from either phosphatidylcholine or phosphatidylethanolamine. Phosphatidylserine localizes to the mitochondria-associated membrane of the endoplasmic reticulum, where it serves a structural role as well as a signaling role. Defects in this gene are a cause of Lenz-Majewski hyperostotic dwarfism. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1297949).
• BP6: Variant 8-96262138-C-G is Benign according to our data. Variant chr8-96262138-C-G is described in ClinVar as [Benign]. Clinvar id is 1500463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTDSS1	NM_014754.3	c.98C>G	p.Thr33Ser	missense_variant	1/13	ENST00000517309.6
PTDSS1	NM_001290225.2	c.-171C>G		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTDSS1	ENST00000517309.6	c.98C>G	p.Thr33Ser	missense_variant	1/13	1	NM_014754.3	P1
PTDSS1	ENST00000337004.8	c.98C>G	p.Thr33Ser	missense_variant, NMD_transcript_variant	1/11	1
PTDSS1	ENST00000517557.5	n.172C>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000358 AC: 9 AN: 251332 Hom.: 0 AF XY: 0.0000294 AC XY: 4 AN XY: 135858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461644 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000340

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 13, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	21
Dann	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.0055
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.060
Sift	Benign	0.57	T
Sift4G	Benign	0.46	T
Polyphen		0.044	B
Vest4		0.18
MutPred		0.47		Loss of catalytic residue at T33 (P = 0.0209);
MVP		0.093
MPC		0.62
ClinPred		0.13	T
GERP RS		4.2
Varity_R		0.40
gMVP		0.80

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

Other links and lift over

dbSNP: rs751925742; hg19: chr8-97274366;