11-6431388-G-C

Variant names:

• chr11-6431388-G-C
• rs74053382
• NM_000613.3:c.1212C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000613.3(HPX):​c.1212C>G​(p.Asp404Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HPX NM_000613.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

Genes affected

HPX (HGNC:5171): (hemopexin) This gene encodes a plasma glycoprotein that binds heme with high affinity. The encoded protein is an acute phase protein that transports heme from the plasma to the liver and may be involved in protecting cells from oxidative stress. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPX	NM_000613.3	c.1212C>G	p.Asp404Glu	missense_variant	Exon 10 of 10	ENST00000265983.8	NP_000604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPX	ENST00000265983.8	c.1212C>G	p.Asp404Glu	missense_variant	Exon 10 of 10	1	NM_000613.3	ENSP00000265983.3
HPX	ENST00000527556.5	n.1040C>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
HPX	ENST00000529037.1	n.*7C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.65		Loss of sheet (P = 0.0126);
MVP		0.29
MPC		0.79
ClinPred		0.99	D
GERP RS		-8.0
Varity_R		0.56
gMVP		0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs74053382; hg19: chr11-6452618;