rs7824505

Variant names:

• chr8-96318463-C-A
• rs7824505
• NM_014754.3:c.1074-1783C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

PTDSS1 Gene-Disease associations (from GenCC):

• Lenz-Majewski hyperostotic dwarfism

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014754.3. 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
	PTDSS1	NM_014754.3	MANE Select	c.1074-1783C>A		intron	N/A	NP_055569.1	P48651-1
	PTDSS1	NM_001290225.2		c.636-1783C>A		intron	N/A	NP_001277154.1	P48651-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTDSS1	ENST00000517309.6	TSL:1 MANE Select	c.1074-1783C>A		intron	N/A	ENSP00000430548.1	P48651-1
	PTDSS1	ENST00000337004.8	TSL:1	n.*577-1783C>A		intron	N/A	ENSP00000337331.4	J3KNR6
	PTDSS1	ENST00000894612.1		c.1074-1783C>A		intron	N/A	ENSP00000564671.1

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

African (AFR) AF: 0.444 AC: 18405 AN: 41438

American (AMR) AF: 0.410 AC: 6267 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3470

East Asian (EAS) AF: 0.0958 AC: 496 AN: 5178

South Asian (SAS) AF: 0.371 AC: 1785 AN: 4808

European-Finnish (FIN) AF: 0.479 AC: 5057 AN: 10552

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32742 AN: 67952

Other (OTH) AF: 0.421 AC: 889 AN: 2114

Alfa AF: 0.435 Hom.: 5262

Bravo AF: 0.443

Asia WGS AF: 0.250 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.66
DANN	Benign	0.65
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs7824505; hg19: chr8-97330691;