rs3213431

Variant names:

• chr12-6839364-T-A
• rs3213431
• NM_014262.5:c.2114T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6839364-T-A
• chr12-6839364-T-C

Variant summary

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

The NM_014262.5(P3H3):​c.2114T>A​(p.Met705Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 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: not found (cov: 32)
• Consequence: P3H3 NM_014262.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 9 publications found

Genes affected

P3H3 (HGNC:19318): (prolyl 3-hydroxylase 3) The protein encoded by this gene belongs to the leprecan family of proteoglycans, which function as collagen prolyl hydroxylases that are required for proper collagen biosynthesis, folding and assembly. This protein, like other family members, is thought to reside in the endoplasmic reticulum. Epigenetic inactivation of this gene is associated with breast and other cancers, suggesting that it may function as a tumor suppressor. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050369292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H3	NM_014262.5	c.2114T>A	p.Met705Lys	missense_variant	Exon 15 of 15	ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.2114T>A	p.Met705Lys	missense_variant	Exon 15 of 15	1	NM_014262.5	ENSP00000478600.1
P3H3	ENST00000612048.4	n.1647T>A		non_coding_transcript_exon_variant	Exon 14 of 14	1
P3H3	ENST00000536140.5	n.2744T>A		non_coding_transcript_exon_variant	Exon 16 of 16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 160148 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	1.8
DANN	Benign	0.74
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.63
REVEL	Benign	0.057
Sift4G	Benign	0.29	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.21		Gain of ubiquitination at M705 (P = 0.0085);
MVP		0.014
ClinPred		0.17	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.66
gMVP		0.31
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3213431; hg19: chr12-6948528;