chrX-24562316-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004845.5(PCYT1B):​c.1087G>A​(p.Glu363Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 1,047,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000067 ( 0 hom. 3 hem. )

Consequence

PCYT1B
NM_004845.5 missense

Scores

4
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34
Variant links:
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 -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCYT1BNM_004845.5 linkc.1087G>A p.Glu363Lys missense_variant Exon 8 of 8 ENST00000379144.7 NP_004836.2 Q9Y5K3-1
PCYT1BNM_001163264.2 linkc.1033G>A p.Glu345Lys missense_variant Exon 8 of 8 NP_001156736.1 Q9Y5K3-4
PCYT1BXM_017029977.2 linkc.799G>A p.Glu267Lys missense_variant Exon 9 of 9 XP_016885466.1
PCYT1BNM_001163265.2 linkc.960+127G>A intron_variant Intron 8 of 8 NP_001156737.1 Q9Y5K3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCYT1BENST00000379144.7 linkc.1087G>A p.Glu363Lys missense_variant Exon 8 of 8 1 NM_004845.5 ENSP00000368439.2 Q9Y5K3-1
PCYT1BENST00000379145.5 linkc.1033G>A p.Glu345Lys missense_variant Exon 8 of 8 1 ENSP00000368440.1 Q9Y5K3-4
PCYT1BENST00000356768.8 linkc.960+127G>A intron_variant Intron 8 of 8 1 ENSP00000349211.4 Q9Y5K3-2
PCYT1BENST00000496020.1 linkn.*396G>A downstream_gene_variant 3 ENSP00000436562.1 F2Z2B1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000668
AC:
7
AN:
1047957
Hom.:
0
Cov.:
30
AF XY:
0.00000898
AC XY:
3
AN XY:
333939
show subpopulations
Gnomad4 AFR exome
AF:
0.0000399
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000734
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000346
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1087G>A (p.E363K) alteration is located in exon 8 (coding exon 8) of the PCYT1B gene. This alteration results from a G to A substitution at nucleotide position 1087, causing the glutamic acid (E) at amino acid position 363 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
0.42
.;N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.83
N;N
REVEL
Benign
0.24
Sift
Uncertain
0.0040
D;D
Sift4G
Benign
0.078
T;T
Polyphen
0.99
.;D
Vest4
0.63
MutPred
0.14
.;Gain of ubiquitination at E363 (P = 0.0039);
MVP
0.75
MPC
2.2
ClinPred
0.98
D
GERP RS
5.9
Varity_R
0.70
gMVP
0.60

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

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

Other links and lift over

dbSNP: rs781320489; hg19: chrX-24580433; COSMIC: COSV100770968; COSMIC: COSV100770968; API