3-189957700-AAGAGAGAGAG-AAG

Variant names:

• chr3-189957700-AAGAGAGAG-A
• rs3062112
• ENST00000319332:c.*204_*211delCTCTCTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018192.4(P3H2):​c.*204_*211delCTCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 543,352 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 0)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00461 (681/147612) while in subpopulation AFR AF= 0.0158 (633/40152). AF 95% confidence interval is 0.0147. There are 3 homozygotes in gnomad4. There are 303 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*204_*211delCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*204_*211delCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332	c.*204_*211delCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335	c.*204_*211delCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2
P3H2	ENST00000490940.1	n.461_468delCTCTCTCT		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 681 AN: 147502 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00224

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: 0.0000898

Gnomad OTH AF: 0.00446

GnomAD4 exome AF: 0.000576 AC: 228 AN: 395740 Hom.: 1 AF XY: 0.000461 AC XY: 98 AN XY: 212616

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000184

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000461

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.00461 AC: 681 AN: 147612 Hom.: 3 Cov.: 0 AF XY: 0.00423 AC XY: 303 AN XY: 71708

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.00224

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000898

Gnomad4 OTH AF: 0.00441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3062112; hg19: chr3-189675489;