Variant X-24562409-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.17

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:

Genome browser will be placed here

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
PCYT1B	NM_004845.5 linkuse as main transcript	c.994C>T	p.Arg332Cys	missense_variant	8/8	ENST00000379144.7
PCYT1B	NM_001163264.2 linkuse as main transcript	c.940C>T	p.Arg314Cys	missense_variant	8/8
PCYT1B	XM_017029977.2 linkuse as main transcript	c.706C>T	p.Arg236Cys	missense_variant	9/9
PCYT1B	NM_001163265.2 linkuse as main transcript	c.960+34C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYT1B	ENST00000379144.7 linkuse as main transcript	c.994C>T	p.Arg332Cys	missense_variant	8/8	1	NM_004845.5	P1	Q9Y5K3-1
PCYT1B	ENST00000379145.5 linkuse as main transcript	c.940C>T	p.Arg314Cys	missense_variant	8/8	1			Q9Y5K3-4
PCYT1B	ENST00000356768.8 linkuse as main transcript	c.960+34C>T		intron_variant		1			Q9Y5K3-2
PCYT1B	ENST00000496020.1 linkuse as main transcript	c.*303C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.0000893

AC:

AN:

111980

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

34136

show subpopulations

Gnomad AFR

AF:

0.000292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000195

AC:

AN:

154109

Hom.:

AF XY:

0.0000672

AC XY:

AN XY:

44625

show subpopulations

Gnomad AFR exome

AF:

0.000161

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:

0.0000143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000557

AC:

AN:

1077624

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

348490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000775

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000398

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000240

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000893

AC:

AN:

111980

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

34136

show subpopulations

Gnomad4 AFR

AF:

0.000292

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000247

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

Cadd

Pathogenic

Dann

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.82

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.0040

.;B

Vest4

0.42

MVP

0.82

MPC

1.8

ClinPred

0.30

GERP RS

4.8

Varity_R

0.51

gMVP

0.65

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