NM_000613.3:c.1018G>C

Variant names:

• chr11-6431752-C-G
• rs548806193
• NM_000613.3:c.1018G>C

Variant summary

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

The NM_000613.3(HPX):​c.1018G>C​(p.Gly340Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 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. G340S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HPX NM_000613.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000613.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPX	NM_000613.3	MANE Select	c.1018G>C	p.Gly340Arg	missense	Exon 9 of 10	NP_000604.1	P02790

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPX	ENST00000265983.8	TSL:1 MANE Select	c.1018G>C	p.Gly340Arg	missense	Exon 9 of 10	ENSP00000265983.3	P02790
	HPX	ENST00000868746.1		c.1015G>C	p.Gly339Arg	missense	Exon 9 of 10	ENSP00000538805.1
	HPX	ENST00000868752.1		c.1009G>C	p.Gly337Arg	missense	Exon 9 of 10	ENSP00000538811.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.0037	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.8
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.68		Gain of MoRF binding (P = 0.0203)
MVP		0.47
MPC		0.90
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.79
gMVP		0.80
Mutation Taster		=59/41	polymorphism

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: rs548806193; hg19: chr11-6452982;