rs371401688

Variant names:

• chr17-41809748-C-G
• rs371401688
• NM_006455.3:c.874G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-41809748-C-G
• chr17-41809748-C-T

Variant summary

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

The NM_006455.3(P3H4):​c.874G>C​(p.Val292Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V292M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: P3H4 NM_006455.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.80
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H4	NM_006455.3	c.874G>C	p.Val292Leu	missense_variant	Exon 4 of 8	ENST00000393928.6	NP_006446.1
P3H4	XM_047435137.1	c.1057G>C	p.Val353Leu	missense_variant	Exon 4 of 8		XP_047291093.1
P3H4	XM_047435138.1	c.1057G>C	p.Val353Leu	missense_variant	Exon 4 of 7		XP_047291094.1
P3H4	XM_006721640.5	c.874G>C	p.Val292Leu	missense_variant	Exon 4 of 7		XP_006721703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H4	ENST00000393928.6	c.874G>C	p.Val292Leu	missense_variant	Exon 4 of 8	1	NM_006455.3	ENSP00000377505.1
P3H4	ENST00000355468.7	c.874G>C	p.Val292Leu	missense_variant	Exon 5 of 9	2		ENSP00000347649.2
P3H4	ENST00000592026.1	c.430+1115G>C		intron_variant	Intron 3 of 4	5		ENSP00000468174.1
P3H4	ENST00000587455.1	n.481+932G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461486 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727040

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
PhyloP100		7.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.25
Sift	Benign	0.47	T;T
Sift4G	Uncertain	0.058	T;T
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.58		Loss of catalytic residue at V292 (P = 0.0666);Loss of catalytic residue at V292 (P = 0.0666);
MVP		0.072
MPC		0.89
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.42
gMVP		0.53
Mutation Taster		=35/65	disease causing

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: rs371401688; hg19: chr17-39966000;