NM_001312673.2:c.-10-7817A>G

Variant names:

• chr3-196278358-T-C
• rs3772109
• NM_001312673.2:c.-10-7817A>G

Variant summary

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

The NM_001312673.2(PCYT1A):​c.-10-7817A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,002 control chromosomes in the GnomAD database, including 11,517 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 0.38 (11517 hom., cov: 31)
• Consequence: PCYT1A NM_001312673.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 5 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

ENSG00000272741 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312673.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1A	NM_001312673.2	MANE Select	c.-10-7817A>G		intron	N/A	NP_001299602.1
	PCYT1A	NM_005017.4		c.-11+5117A>G		intron	N/A	NP_005008.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1A	ENST00000431016.6	TSL:1 MANE Select	c.-10-7817A>G		intron	N/A	ENSP00000394617.1
	PCYT1A	ENST00000292823.6	TSL:1	c.-11+5117A>G		intron	N/A	ENSP00000292823.2
	ENSG00000272741	ENST00000431391.1	TSL:5	n.318-7817A>G		intron	N/A	ENSP00000405181.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57179 AN: 151884 Hom.: 11487 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.377 AC: 57263 AN: 152002 Hom.: 11517 Cov.: 31 AF XY: 0.379 AC XY: 28152 AN XY: 74310

African (AFR) AF: 0.374 AC: 15511 AN: 41440

American (AMR) AF: 0.456 AC: 6965 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3466

East Asian (EAS) AF: 0.813 AC: 4204 AN: 5170

South Asian (SAS) AF: 0.361 AC: 1739 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2984 AN: 10558

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23625 AN: 67968

Other (OTH) AF: 0.378 AC: 799 AN: 2114

Alfa AF: 0.367 Hom.: 1858

Bravo AF: 0.394

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

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: rs3772109; hg19: chr3-196005229;