Variant 8-96273389-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001290225.2(PTDSS1):c.2T>C(p.Met1?) variant causes a start lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,603,590 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

PTDSS1
NM_001290225.2 start_lost, splice_region

Scores

Splicing: ADA: 0.00004883

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.772

Variant links:

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 links:

PTDSS1 (HGNC:):

PTDSS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-96273389-T-C is Benign according to our data. Variant chr8-96273389-T-C is described in ClinVar as [Benign]. Clinvar id is 776364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-96273389-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1675/152340) while in subpopulation AFR AF= 0.0384 (1598/41582). AF 95% confidence interval is 0.0369. There are 31 homozygotes in gnomad4. There are 779 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1675 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTDSS1	NM_014754.3 linkuse as main transcript	c.270T>C	p.Asn90Asn	splice_region_variant, synonymous_variant	2/13	ENST00000517309.6	NP_055569.1	P48651-1
PTDSS1	NM_001290225.2 linkuse as main transcript	c.2T>C	p.Met1?	start_lost, splice_region_variant	2/11		NP_001277154.1	P48651-2
LOC105375652	XR_928431.3 linkuse as main transcript	n.91-7052A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTDSS1	ENST00000517309.6 linkuse as main transcript	c.270T>C	p.Asn90Asn	splice_region_variant, synonymous_variant	2/13	1	NM_014754.3	ENSP00000430548.1	P48651-1
PTDSS1	ENST00000337004.8 linkuse as main transcript	n.270T>C		splice_region_variant, non_coding_transcript_exon_variant	2/11	1		ENSP00000337331.4	J3KNR6
PTDSS1	ENST00000517557.5 linkuse as main transcript	n.344T>C		splice_region_variant, non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1673

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00292

AC:

718

AN:

245522

Hom.:

AF XY:

0.00227

AC XY:

301

AN XY:

132596

show subpopulations

Gnomad AFR exome

AF:

0.0395

Gnomad AMR exome

AF:

0.00221

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:

0.0000178

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.00107

AC:

1555

AN:

1451250

Hom.:

Cov.:

AF XY:

0.000933

AC XY:

674

AN XY:

722276

show subpopulations

Gnomad4 AFR exome

AF:

0.0388

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000335

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.0110

AC:

1675

AN:

152340

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

779

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0384

Gnomad4 AMR

AF:

0.00385

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.5

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over