rs782133230

Variant names:

• chr17-41806842-C-A
• rs782133230
• NM_006455.3:c.1100G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41806842-C-A
• chr17-41806842-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006455.3(P3H4):​c.1100G>T​(p.Arg367Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R367Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: P3H4 NM_006455.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 0 publications found

Genes affected

P3H4 (HGNC:16946): (prolyl 3-hydroxylase family member 4 (inactive)) This nucleolar protein was first characterized because it was an autoantigen in cases on interstitial cystitis. The protein, with a predicted molecular weight of 50 kDa, appears to be localized in the particulate compartment of the interphase nucleolus, with a distribution distinct from that of nucleolar protein B23. During mitosis it is associated with chromosomes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16370803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H4	NM_006455.3	c.1100G>T	p.Arg367Leu	missense_variant	Exon 6 of 8	ENST00000393928.6	NP_006446.1
P3H4	XM_047435137.1	c.1283G>T	p.Arg428Leu	missense_variant	Exon 6 of 8		XP_047291093.1
P3H4	XM_047435138.1	c.1283G>T	p.Arg428Leu	missense_variant	Exon 6 of 7		XP_047291094.1
P3H4	XM_006721640.5	c.1100G>T	p.Arg367Leu	missense_variant	Exon 6 of 7		XP_006721703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H4	ENST00000393928.6	c.1100G>T	p.Arg367Leu	missense_variant	Exon 6 of 8	1	NM_006455.3	ENSP00000377505.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		0.20
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.052
Sift	Benign	0.081	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.33	B;B
Vest4		0.31
MutPred		0.40		Loss of disorder (P = 0.0699);Loss of disorder (P = 0.0699);
MVP		0.12
MPC		0.52
ClinPred		0.86	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.33

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: rs782133230; hg19: chr17-39963094; COSMIC: COSV100821215; COSMIC: COSV100821215;