3-190120238-C-T

Variant names:

• chr3-190120238-C-T
• rs1225591004
• NM_018192.4:c.480+14G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018192.4(P3H2):​c.480+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.284
• Publications: 0 publications found

Genes affected

P3H2 (HGNC:19317): (prolyl 3-hydroxylase 2) This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

P3H2-AS1 (HGNC:40886): (P3H2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-190120238-C-T is Benign according to our data. Variant chr3-190120238-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1672075.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018192.4. 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
	P3H2	NM_018192.4	MANE Select	c.480+14G>A		intron	N/A	NP_060662.2
	P3H2	NM_001134418.2		c.-64+1965G>A		intron	N/A	NP_001127890.1	Q8IVL5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	ENST00000319332.10	TSL:1 MANE Select	c.480+14G>A		intron	N/A	ENSP00000316881.5	Q8IVL5-1
	P3H2	ENST00000427335.6	TSL:1	c.-64+1965G>A		intron	N/A	ENSP00000408947.2	Q8IVL5-2
	P3H2	ENST00000895815.1		c.480+14G>A		intron	N/A	ENSP00000565874.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454950 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723004

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 84840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4968

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109824

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.3
DANN	Benign	0.76
PhyloP100		0.28

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: rs1225591004; hg19: chr3-189838027;