rs7824505

chr8-96318463-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014754.3(PTDSS1):c.1074-1783C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,004 control chromosomes in the GnomAD database, including 15,700 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 0.45 (15700 hom., cov: 32)
• Consequence: PTDSS1 NM_014754.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTDSS1	NM_014754.3	c.1074-1783C>A		intron_variant		ENST00000517309.6
PTDSS1	NM_001290225.2	c.636-1783C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTDSS1	ENST00000517309.6	c.1074-1783C>A		intron_variant		1	NM_014754.3	P1
PTDSS1	ENST00000337004.8	c.*577-1783C>A		intron_variant, NMD_transcript_variant		1
PTDSS1	ENST00000522072.1	c.465-1783C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67777 AN: 151886 Hom.: 15697 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.424

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67793 AN: 152004 Hom.: 15700 Cov.: 32 AF XY: 0.442 AC XY: 32844 AN XY: 74270

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.0958

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.421

Alfa AF: 0.445 Hom.: 2817

Bravo AF: 0.443

Asia WGS AF: 0.250 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.66
Dann	Benign	0.65

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: rs7824505; hg19: chr8-97330691;