chrX-24562409-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004845.5(PCYT1B):c.994C>T(p.Arg332Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,189,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 22)
Exomes 𝑓: 0.0000056 ( 0 hom. 5 hem. )
Consequence
PCYT1B
NM_004845.5 missense
NM_004845.5 missense
Scores
4
5
6
Clinical Significance
Conservation
PhyloP100: 9.17
Genes affected
PCYT1B (HGNC:8755): (phosphate cytidylyltransferase 1B, choline) The protein encoded by this gene belongs to the cytidylyltransferase family. It is involved in the regulation of phosphatidylcholine biosynthesis. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20072296).
BS2
?
High Hemizygotes in GnomAd at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCYT1B | NM_004845.5 | c.994C>T | p.Arg332Cys | missense_variant | 8/8 | ENST00000379144.7 | |
PCYT1B | NM_001163264.2 | c.940C>T | p.Arg314Cys | missense_variant | 8/8 | ||
PCYT1B | XM_017029977.2 | c.706C>T | p.Arg236Cys | missense_variant | 9/9 | ||
PCYT1B | NM_001163265.2 | c.960+34C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCYT1B | ENST00000379144.7 | c.994C>T | p.Arg332Cys | missense_variant | 8/8 | 1 | NM_004845.5 | P1 | |
PCYT1B | ENST00000379145.5 | c.940C>T | p.Arg314Cys | missense_variant | 8/8 | 1 | |||
PCYT1B | ENST00000356768.8 | c.960+34C>T | intron_variant | 1 | |||||
PCYT1B | ENST00000496020.1 | c.*303C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000893 AC: 10AN: 111980Hom.: 0 Cov.: 22 AF XY: 0.0000879 AC XY: 3AN XY: 34136
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GnomAD3 exomes AF: 0.0000195 AC: 3AN: 154109Hom.: 0 AF XY: 0.0000672 AC XY: 3AN XY: 44625
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GnomAD4 exome AF: 0.00000557 AC: 6AN: 1077624Hom.: 0 Cov.: 30 AF XY: 0.0000143 AC XY: 5AN XY: 348490
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2024 | The c.994C>T (p.R332C) alteration is located in exon 8 (coding exon 8) of the PCYT1B gene. This alteration results from a C to T substitution at nucleotide position 994, causing the arginine (R) at amino acid position 332 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.0040
.;B
Vest4
MVP
MPC
1.8
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