Variant chr16-72076578-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_020995.4(HPR):c.544C>G(p.Pro182Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HPR
NM_020995.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

HPR (HGNC:5156): (haptoglobin-related protein) This gene encodes a haptoglobin-related protein that binds hemoglobin as efficiently as haptoglobin. Unlike haptoglobin, plasma concentration of this protein is unaffected in patients with sickle cell anemia and extensive intravascular hemolysis, suggesting a difference in binding between haptoglobin-hemoglobin and haptoglobin-related protein-hemoglobin complexes to CD163, the hemoglobin scavenger receptor. This protein may also be a clinically important predictor of recurrence of breast cancer. [provided by RefSeq, Oct 2011]

HPR links:

TXNL4B (HGNC:):

TXNL4B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPR	NM_020995.4 linkuse as main transcript	c.544C>G	p.Pro182Ala	missense_variant	5/5	ENST00000540303.7	NP_066275.3	P00739-1
HPR	NM_001384360.1 linkuse as main transcript	c.184C>G	p.Pro62Ala	missense_variant	6/6		NP_001371289.1
HPR	XM_024450251.2 linkuse as main transcript	c.562C>G	p.Pro188Ala	missense_variant	5/5		XP_024306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPR	ENST00000540303.7 linkuse as main transcript	c.544C>G	p.Pro182Ala	missense_variant	5/5	1	NM_020995.4	ENSP00000441828.2		P00739-1
TXNL4B	ENST00000562153.5 linkuse as main transcript	c.284+12409G>C		intron_variant		4		ENSP00000454635.2		H3BN11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.544C>G (p.P182A) alteration is located in exon 5 (coding exon 5) of the HPR gene. This alteration results from a C to G substitution at nucleotide position 544, causing the proline (P) at amino acid position 182 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.79

D;T

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.7

D;.

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.031

D;D

Polyphen

1.0

D;.

Vest4

0.63

MutPred

0.91

Loss of methylation at K177 (P = 0.0979);.;

MVP

0.90

MPC

0.48

ClinPred

1.0

GERP RS

2.5

Varity_R

0.90

gMVP

0.52

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over