3-196214345-C-A

Position:

• chr3-196214345-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000441879.5(PCYT1A):​c.515G>T​(p.Arg172Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/10 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 0.0000066 (0 hom., cov: 31)
• Consequence: PCYT1A ENST00000441879.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606

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]

LOC105374304 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33247173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374304	XR_001740542.2	n.2192G>T		non_coding_transcript_exon_variant	4/5
LOC105374304	XR_001740545.2	n.1422G>T		non_coding_transcript_exon_variant	3/4
LOC105374304	XR_001740546.2	n.447G>T		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCYT1A	ENST00000441879.5	c.515G>T	p.Arg172Met	missense_variant	6/6	3		ENSP00000392397.1
SLC51A	ENST00000416660.1	c.-47-78C>A		intron_variant		4		ENSP00000405414.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151824 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151824 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74130

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.8
DANN	Benign	0.74
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00070	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.90	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.058
Sift	Uncertain	0.0040	D
MutPred		0.70		Loss of methylation at K173 (P = 0.0231);
MVP		0.18
ClinPred		0.13	T
GERP RS		0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7642243; hg19: chr3-195941216;