8-96273201-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014754.3(PTDSS1):c.180-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 749,250 control chromosomes in the GnomAD database, including 3,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1396 hom., cov: 32)
  • Exomes 𝑓: 0.075 (2115 hom.)
• Consequence: PTDSS1 NM_014754.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

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]

LOC105375652 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-96273201-G-A is Benign according to our data. Variant chr8-96273201-G-A is described in ClinVar as [Benign]. Clinvar id is 1228596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTDSS1	NM_014754.3	c.180-98G>A		intron_variant		ENST00000517309.6
LOC105375652	XR_928431.3	n.91-6864C>T		intron_variant, non_coding_transcript_variant
PTDSS1	NM_001290225.2	c.-89-98G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTDSS1	ENST00000517309.6	c.180-98G>A		intron_variant		1	NM_014754.3	P1
PTDSS1	ENST00000337004.8	c.180-98G>A		intron_variant, NMD_transcript_variant		1
PTDSS1	ENST00000517557.5	n.254-98G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17413 AN: 152054 Hom.: 1387 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0429

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0752 AC: 44912 AN: 597076 Hom.: 2115 AF XY: 0.0743 AC XY: 23203 AN XY: 312166

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.000219

Gnomad4 SAS exome AF: 0.0530

Gnomad4 FIN exome AF: 0.0477

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.0843

GnomAD4 genome AF: 0.115 AC: 17445 AN: 152174 Hom.: 1396 Cov.: 32 AF XY: 0.110 AC XY: 8217 AN XY: 74408

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0465

Gnomad4 FIN AF: 0.0429

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0983 Hom.: 216

Bravo AF: 0.122

Asia WGS AF: 0.0380 AC: 133 AN: 3478

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.13
Dann	Benign	0.19

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: rs16894393; hg19: chr8-97285429;