X-24590181-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004845.5(PCYT1B):c.335-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000916 in 1,091,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000092 (0 hom. 4 hem.)
• Consequence: PCYT1B NM_004845.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002871
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.711

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant X-24590181-C-T is Benign according to our data. Variant chrX-24590181-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2673220.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCYT1B	NM_004845.5	c.335-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000379144.7
PCYT1B	NM_001163264.2	c.281-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
PCYT1B	NM_001163265.2	c.335-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
PCYT1B	XM_017029977.2	c.47-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYT1B	ENST00000379144.7	c.335-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004845.5	P1
PCYT1B	ENST00000356768.8	c.335-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
PCYT1B	ENST00000379145.5	c.281-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
PCYT1B	ENST00000496020.1	c.257-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000112 AC: 2 AN: 177782 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 62622

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000250

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000916 AC: 10 AN: 1091892 Hom.: 0 Cov.: 28 AF XY: 0.0000112 AC XY: 4 AN XY: 357500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000941

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.0000654

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

PCYT1B: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	6.6
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.030		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: rs756525408; hg19: chrX-24608298;