3-196214345-C-G

Variant names:

• chr3-196214345-C-G
• rs7642243
• ENST00000441879.5:c.515G>C
• PCYT1A p.Arg172Thr

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441879.5(PCYT1A):​c.515G>C​(p.Arg172Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 456,616 control chromosomes in the GnomAD database, including 89,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29029 hom., cov: 31)
  • Exomes 𝑓: 0.62 (60130 hom.)
• Consequence: PCYT1A ENST00000441879.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 20 publications found

Genes affected

PCYT1A (HGNC:8754): (phosphate cytidylyltransferase 1A, choline) This gene belongs to the cytidylyltransferase family and is involved in the regulation of phosphatidylcholine biosynthesis. Mutations in this gene are associated with spondylometaphyseal dysplasia with cone-rod dystrophy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

SLC51A (HGNC:29955): (solute carrier family 51 member A) Predicted to enable protein heterodimerization activity; protein homodimerization activity; and transmembrane transporter activity. Involved in bile acid secretion. Located in basolateral plasma membrane. Implicated in progressive familial intrahepatic cholestasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC51A Gene-Disease associations (from GenCC):

• cholestasis, progressive familial intrahepatic, 6

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

LOC105374304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0229578E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441879.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1A	ENST00000441879.5	TSL:3	c.515G>C	p.Arg172Thr	missense	Exon 6 of 6	ENSP00000392397.1	C9J2E1
	SLC51A	ENST00000416660.1	TSL:4	c.-47-78C>G		intron	N/A	ENSP00000405414.1	C9J2I5
	ENSG00000309772	ENST00000843822.1		n.229-434G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93274 AN: 151738 Hom.: 29002 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.587

GnomAD2 exomes AF: 0.645 AC: 89282 AN: 138364 AF XY: 0.647

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.942

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.623 AC: 189828 AN: 304762 Hom.: 60130 Cov.: 0 AF XY: 0.629 AC XY: 109082 AN XY: 173510

African (AFR) AF: 0.635 AC: 5476 AN: 8630

American (AMR) AF: 0.665 AC: 18141 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 6323 AN: 10790

East Asian (EAS) AF: 0.944 AC: 8698 AN: 9210

South Asian (SAS) AF: 0.691 AC: 41271 AN: 59744

European-Finnish (FIN) AF: 0.605 AC: 7844 AN: 12964

Middle Eastern (MID) AF: 0.516 AC: 1432 AN: 2776

European-Non Finnish (NFE) AF: 0.578 AC: 91972 AN: 159026

Other (OTH) AF: 0.605 AC: 8671 AN: 14340

GnomAD4 genome AF: 0.615 AC: 93354 AN: 151854 Hom.: 29029 Cov.: 31 AF XY: 0.619 AC XY: 45933 AN XY: 74202

African (AFR) AF: 0.628 AC: 26002 AN: 41400

American (AMR) AF: 0.638 AC: 9714 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2010 AN: 3466

East Asian (EAS) AF: 0.933 AC: 4818 AN: 5166

South Asian (SAS) AF: 0.712 AC: 3431 AN: 4818

European-Finnish (FIN) AF: 0.617 AC: 6505 AN: 10542

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39104 AN: 67924

Other (OTH) AF: 0.589 AC: 1240 AN: 2104

Alfa AF: 0.518 Hom.: 2700

Bravo AF: 0.617

Asia WGS AF: 0.790 AC: 2748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.3
DANN	Benign	0.47
DEOGEN2	Uncertain	0.63	D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000080	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.61
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.036
Sift	Uncertain	0.013	D
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7642243;

hg19: chr3-195941216;