rs782520454

Variant names:

• chr17-41807972-C-A
• rs782520454
• NM_006455.3:c.949G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41807972-C-A
• chr17-41807972-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.949G>T​(p.Ala317Ser) 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. 16/22 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. A317T) 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: 2.10
• Publications: 2 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=0.22585708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H4	NM_006455.3	c.949G>T	p.Ala317Ser	missense_variant	Exon 5 of 8	ENST00000393928.6	NP_006446.1
P3H4	XM_047435137.1	c.1132G>T	p.Ala378Ser	missense_variant	Exon 5 of 8		XP_047291093.1
P3H4	XM_047435138.1	c.1132G>T	p.Ala378Ser	missense_variant	Exon 5 of 7		XP_047291094.1
P3H4	XM_006721640.5	c.949G>T	p.Ala317Ser	missense_variant	Exon 5 of 7		XP_006721703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H4	ENST00000393928.6	c.949G>T	p.Ala317Ser	missense_variant	Exon 5 of 8	1	NM_006455.3	ENSP00000377505.1
P3H4	ENST00000355468.7	c.949G>T	p.Ala317Ser	missense_variant	Exon 6 of 9	2		ENSP00000347649.2
P3H4	ENST00000592026.1	c.463G>T	p.Ala155Ser	missense_variant	Exon 4 of 5	5		ENSP00000468174.1
P3H4	ENST00000587455.1	n.482-1093G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		2.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.11
Sift	Benign	0.40	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.78	P;P
Vest4		0.35
MutPred		0.35		Gain of disorder (P = 0.0226);Gain of disorder (P = 0.0226);
MVP		0.048
MPC		0.53
ClinPred		0.63	D
GERP RS		3.2
Varity_R		0.14
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782520454; hg19: chr17-39964224;