Genetic Variant PCYT1B:p.Pro58Thr (chrX-24619030-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004845.5(PCYT1B):c.172C>A(p.Pro58Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,074,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000023 ( 0 hom. 12 hem. )

Consequence

PCYT1B
NM_004845.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.46

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=0.113711715).

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYT1B	NM_004845.5 link	c.172C>A	p.Pro58Thr	missense_variant	Exon 2 of 8	ENST00000379144.7	NP_004836.2	Q9Y5K3-1
PCYT1B	NM_001163264.2 link	c.118C>A	p.Pro40Thr	missense_variant	Exon 2 of 8		NP_001156736.1	Q9Y5K3-4
PCYT1B	NM_001163265.2 link	c.172C>A	p.Pro58Thr	missense_variant	Exon 2 of 9		NP_001156737.1	Q9Y5K3-2
PCYT1B	XM_017029977.2 link	c.-117C>A		5_prime_UTR_variant	Exon 3 of 9		XP_016885466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCYT1B	ENST00000379144.7 link	c.172C>A	p.Pro58Thr	missense_variant	Exon 2 of 8	1	NM_004845.5	ENSP00000368439.2	Q9Y5K3-1
PCYT1B	ENST00000379145.5 link	c.118C>A	p.Pro40Thr	missense_variant	Exon 2 of 8	1		ENSP00000368440.1	Q9Y5K3-4
PCYT1B	ENST00000356768.8 link	c.172C>A	p.Pro58Thr	missense_variant	Exon 2 of 9	1		ENSP00000349211.4	Q9Y5K3-2
PCYT1B	ENST00000496020.1 link	n.94C>A		non_coding_transcript_exon_variant	Exon 2 of 7	3		ENSP00000436562.1	F2Z2B1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000788

AC:

AN:

165022

Hom.:

AF XY:

0.000115

AC XY:

AN XY:

52346

show subpopulations

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:

0.000956

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1074571

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

345107

show subpopulations

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:

0.000444

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172C>A (p.P58T) alteration is located in exon 2 (coding exon 2) of the PCYT1B gene. This alteration results from a C to A substitution at nucleotide position 172, causing the proline (P) at amino acid position 58 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Benign

0.10

.;.;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

2.0

.;M;M

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.080

N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0020, 0.0030

.;B;B

Vest4

0.40

MutPred

0.38

.;Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);

MVP

0.84

MPC

0.0028

ClinPred

0.29

GERP RS

5.0

Varity_R

0.29

gMVP

0.77

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