rs375775038

Variant names:

• chr17-41806852-C-A
• rs375775038
• NM_006455.3:c.1090G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41806852-C-A
• chr17-41806852-C-T

Variant summary

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

The NM_006455.3(P3H4):​c.1090G>T​(p.Ala364Ser) 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. A364T) 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: -0.264
• Publications: 1 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: 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=0.044617742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H4	NM_006455.3	c.1090G>T	p.Ala364Ser	missense_variant	Exon 6 of 8	ENST00000393928.6	NP_006446.1
P3H4	XM_047435137.1	c.1273G>T	p.Ala425Ser	missense_variant	Exon 6 of 8		XP_047291093.1
P3H4	XM_047435138.1	c.1273G>T	p.Ala425Ser	missense_variant	Exon 6 of 7		XP_047291094.1
P3H4	XM_006721640.5	c.1090G>T	p.Ala364Ser	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.1090G>T	p.Ala364Ser	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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.85
DANN	Benign	0.89
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.52	N;N
PhyloP100		-0.26
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.0090
Sift	Benign	0.32	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0030	B;B
Vest4		0.21
MutPred		0.25		Gain of disorder (P = 0.0631);Gain of disorder (P = 0.0631);
MVP		0.014
MPC		0.24
ClinPred		0.041	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.062

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: rs375775038; hg19: chr17-39963104;