8-96273333-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2
The NM_014754.3(PTDSS1):c.214G>A(p.Gly72Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00127 in 1,612,336 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 3 hom. )
Consequence
PTDSS1
NM_014754.3 missense
NM_014754.3 missense
Scores
7
7
5
Clinical Significance
Conservation
PhyloP100: 6.65
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.35919198).
BP6
Variant 8-96273333-G-A is Benign according to our data. Variant chr8-96273333-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 156 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTDSS1 | NM_014754.3 | c.214G>A | p.Gly72Ser | missense_variant | 2/13 | ENST00000517309.6 | NP_055569.1 | |
PTDSS1 | NM_001290225.2 | c.-55G>A | 5_prime_UTR_variant | 2/11 | NP_001277154.1 | |||
LOC105375652 | XR_928431.3 | n.91-6996C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTDSS1 | ENST00000517309.6 | c.214G>A | p.Gly72Ser | missense_variant | 2/13 | 1 | NM_014754.3 | ENSP00000430548.1 | ||
PTDSS1 | ENST00000337004.8 | n.214G>A | non_coding_transcript_exon_variant | 2/11 | 1 | ENSP00000337331.4 | ||||
PTDSS1 | ENST00000517557.5 | n.288G>A | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00103 AC: 156AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000822 AC: 205AN: 249458Hom.: 0 AF XY: 0.000815 AC XY: 110AN XY: 134890
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GnomAD4 exome AF: 0.00129 AC: 1885AN: 1460054Hom.: 3 Cov.: 30 AF XY: 0.00122 AC XY: 885AN XY: 726338
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GnomAD4 genome AF: 0.00102 AC: 156AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000860 AC XY: 64AN XY: 74456
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 09, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at