rs7639752

Variant names:

• chr3-196246373-G-A
• rs7639752
• NM_001312673.2:c.486+994C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-196246373-G-A
• chr3-196246373-G-C
• chr3-196246373-G-T

Variant summary

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

The NM_001312673.2(PCYT1A):​c.486+994C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,220 control chromosomes in the GnomAD database, including 18,110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18110 hom., cov: 29)
• Consequence: PCYT1A NM_001312673.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 16 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]

PCYT1A Gene-Disease associations (from GenCC):

• spondylometaphyseal dysplasia-cone-rod dystrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYT1A	NM_001312673.2	c.486+994C>T		intron_variant	Intron 5 of 8	ENST00000431016.6	NP_001299602.1
PCYT1A	NM_005017.4	c.486+994C>T		intron_variant	Intron 6 of 9		NP_005008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCYT1A	ENST00000431016.6	c.486+994C>T		intron_variant	Intron 5 of 8	1	NM_001312673.2	ENSP00000394617.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72536 AN: 151128 Hom.: 18092 Cov.: 29

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.480 AC: 72594 AN: 151220 Hom.: 18110 Cov.: 29 AF XY: 0.484 AC XY: 35764 AN XY: 73834

African (AFR) AF: 0.390 AC: 16021 AN: 41104

American (AMR) AF: 0.550 AC: 8378 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3466

East Asian (EAS) AF: 0.887 AC: 4583 AN: 5164

South Asian (SAS) AF: 0.552 AC: 2636 AN: 4774

European-Finnish (FIN) AF: 0.450 AC: 4656 AN: 10354

Middle Eastern (MID) AF: 0.451 AC: 130 AN: 288

European-Non Finnish (NFE) AF: 0.490 AC: 33226 AN: 67844

Other (OTH) AF: 0.481 AC: 1006 AN: 2092

Alfa AF: 0.486 Hom.: 55703

Bravo AF: 0.485

Asia WGS AF: 0.687 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7639752; hg19: chr3-195973244;