NM_004845.5:c.994C>T

Variant names:

• chrX-24562409-G-A
• rs745805932
• NM_004845.5:c.994C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.17
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20072296).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1B	NM_004845.5	MANE Select	c.994C>T	p.Arg332Cys	missense	Exon 8 of 8	NP_004836.2
	PCYT1B	NM_001163264.2		c.940C>T	p.Arg314Cys	missense	Exon 8 of 8	NP_001156736.1	Q9Y5K3-4
	PCYT1B	NM_001163265.2		c.960+34C>T		intron	N/A	NP_001156737.1	Q9Y5K3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1B	ENST00000379144.7	TSL:1 MANE Select	c.994C>T	p.Arg332Cys	missense	Exon 8 of 8	ENSP00000368439.2	Q9Y5K3-1
	PCYT1B	ENST00000379145.5	TSL:1	c.940C>T	p.Arg314Cys	missense	Exon 8 of 8	ENSP00000368440.1	Q9Y5K3-4
	PCYT1B	ENST00000356768.8	TSL:1	c.960+34C>T		intron	N/A	ENSP00000349211.4	Q9Y5K3-2

Frequencies

GnomAD3 genomes AF: 0.0000893 AC: 10 AN: 111980 Hom.: 0 Cov.: 22

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

GnomAD2 exomes AF: 0.0000195 AC: 3 AN: 154109 AF XY: 0.0000672

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000143

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000557 AC: 6 AN: 1077624 Hom.: 0 Cov.: 30 AF XY: 0.0000143 AC XY: 5 AN XY: 348490

African (AFR) AF: 0.0000775 AC: 2 AN: 25793

American (AMR) AF: 0.00 AC: 0 AN: 32002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18040

East Asian (EAS) AF: 0.00 AC: 0 AN: 30024

South Asian (SAS) AF: 0.0000398 AC: 2 AN: 50234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39767

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 0.00000240 AC: 2 AN: 832549

Other (OTH) AF: 0.00 AC: 0 AN: 45221

GnomAD4 genome AF: 0.0000893 AC: 10 AN: 111980 Hom.: 0 Cov.: 22 AF XY: 0.0000879 AC XY: 3 AN XY: 34136

African (AFR) AF: 0.000292 AC: 9 AN: 30822

American (AMR) AF: 0.00 AC: 0 AN: 10587

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3552

South Asian (SAS) AF: 0.00 AC: 0 AN: 2712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53144

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.039	D
Polyphen		0.0040	B
Vest4		0.42
MVP		0.82
MPC		1.8
ClinPred		0.30	T
GERP RS		4.8
Varity_R		0.51
gMVP		0.65
Mutation Taster		=41/59	disease causing

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

Other links and lift over

dbSNP: rs745805932; hg19: chrX-24580526;