X-24562471-A-G

Variant names:

• chrX-24562471-A-G
• NM_004845.5:c.932T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004845.5(PCYT1B):​c.932T>C​(p.Leu311Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PCYT1B NM_004845.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYT1B	NM_004845.5	c.932T>C	p.Leu311Pro	missense_variant	Exon 8 of 8	ENST00000379144.7	NP_004836.2
PCYT1B	NM_001163264.2	c.878T>C	p.Leu293Pro	missense_variant	Exon 8 of 8		NP_001156736.1
PCYT1B	NM_001163265.2	c.932T>C	p.Leu311Pro	missense_variant	Exon 8 of 9		NP_001156737.1
PCYT1B	XM_017029977.2	c.644T>C	p.Leu215Pro	missense_variant	Exon 9 of 9		XP_016885466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCYT1B	ENST00000379144.7	c.932T>C	p.Leu311Pro	missense_variant	Exon 8 of 8	1	NM_004845.5	ENSP00000368439.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.932T>C (p.L311P) alteration is located in exon 8 (coding exon 8) of the PCYT1B gene. This alteration results from a T to C substitution at nucleotide position 932, causing the leucine (L) at amino acid position 311 to be replaced by a proline (P). 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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;.;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Uncertain	0.55
Sift	Benign	0.035	D;T;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.66, 0.98	.;P;D
Vest4		0.74
MutPred		0.33		.;Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.90
MPC		2.8
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.91
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-24580588;