Genetic Variant PCYT1B:p.Pro347Pro (chrX-24562362-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004845.5(PCYT1B):c.1041C>T(p.Pro347Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000841 in 1,175,999 control chromosomes in the GnomAD database, including 1 homozygotes. There are 299 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.00087 ( 1 hom. 283 hem. )

Consequence

PCYT1B
NM_004845.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.453

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]

PCYT1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-24562362-G-A is Benign according to our data. Variant chrX-24562362-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660193.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.453 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYT1B	NM_004845.5 link	c.1041C>T	p.Pro347Pro	synonymous_variant	Exon 8 of 8	ENST00000379144.7	NP_004836.2	Q9Y5K3-1
PCYT1B	NM_001163264.2 link	c.987C>T	p.Pro329Pro	synonymous_variant	Exon 8 of 8		NP_001156736.1	Q9Y5K3-4
PCYT1B	XM_017029977.2 link	c.753C>T	p.Pro251Pro	synonymous_variant	Exon 9 of 9		XP_016885466.1
PCYT1B	NM_001163265.2 link	c.960+81C>T		intron_variant	Intron 8 of 8		NP_001156737.1	Q9Y5K3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCYT1B	ENST00000379144.7 link	c.1041C>T	p.Pro347Pro	synonymous_variant	Exon 8 of 8	1	NM_004845.5	ENSP00000368439.2	Q9Y5K3-1
PCYT1B	ENST00000379145.5 link	c.987C>T	p.Pro329Pro	synonymous_variant	Exon 8 of 8	1		ENSP00000368440.1	Q9Y5K3-4
PCYT1B	ENST00000356768.8 link	c.960+81C>T		intron_variant	Intron 8 of 8	1		ENSP00000349211.4	Q9Y5K3-2
PCYT1B	ENST00000496020.1 link	n.*350C>T		downstream_gene_variant		3		ENSP00000436562.1	F2Z2B1

Frequencies

GnomAD3 genomes

AF:

0.000555

AC:

AN:

111732

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

AN XY:

33902

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000372

Gnomad FIN

AF:

0.000494

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000562

AC:

AN:

145962

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

42652

show subpopulations

Gnomad AFR exome

AF:

0.000244

Gnomad AMR exome

AF:

0.000447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000924

Gnomad FIN exome

AF:

0.000531

Gnomad NFE exome

AF:

0.000885

Gnomad OTH exome

AF:

0.000573

GnomAD4 exome

AF:

0.000871

AC:

927

AN:

1064214

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

283

AN XY:

342836

show subpopulations

Gnomad4 AFR exome

AF:

0.000197

Gnomad4 AMR exome

AF:

0.000554

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000627

Gnomad4 FIN exome

AF:

0.000538

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000964

GnomAD4 genome

AF:

0.000555

AC:

AN:

111785

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

33965

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000374

Gnomad4 FIN

AF:

0.000494

Gnomad4 NFE

AF:

0.000810

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000696

Hom.:

Bravo

AF:

0.000793

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PCYT1B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.8

DANN

Benign

0.62

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.

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