Genetic Variant HEBP2:p.Pro23Arg (chr6-138404563-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_014320.3(HEBP2):c.68C>G(p.Pro23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P23L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HEBP2
NM_014320.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.916

Publications

0 publications found

Variant links:

Genes affected

HEBP2 (HGNC:15716): (heme binding protein 2) The protein encoded by this gene is found predominately in the cytoplasm, where it plays a role in the collapse of mitochondrial membrane potential (MMP) prior to necrotic cell death. The encoded protein enhances outer and inner mitochondrial membrane permeabilization, especially under conditions of oxidative stress. [provided by RefSeq, May 2016]

HEBP2 links:

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ACMG classification

Classification was made for transcript

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_014320.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEBP2	NM_014320.3	MANE Select	c.68C>G	p.Pro23Arg	missense	Exon 1 of 4	NP_055135.1	Q9Y5Z4-1
HEBP2	NM_001326381.2		c.68C>G	p.Pro23Arg	missense	Exon 1 of 4	NP_001313310.1	Q5THN1
HEBP2	NM_001326380.2		c.136-582C>G		intron	N/A	NP_001313309.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEBP2	ENST00000607197.6	TSL:1 MANE Select	c.68C>G	p.Pro23Arg	missense	Exon 1 of 4	ENSP00000475750.1	Q9Y5Z4-1
HEBP2	ENST00000858693.1		c.68C>G	p.Pro23Arg	missense	Exon 1 of 5	ENSP00000528752.1
HEBP2	ENST00000367697.7	TSL:2	c.68C>G	p.Pro23Arg	missense	Exon 1 of 4	ENSP00000356670.3	Q5THN1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1158082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

559334

African (AFR)

AF:

0.00

AC:

AN:

23576

American (AMR)

AF:

0.00

AC:

AN:

11126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16504

East Asian (EAS)

AF:

0.00

AC:

AN:

27016

South Asian (SAS)

AF:

0.00

AC:

AN:

42692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3166

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

961274

Other (OTH)

AF:

0.00

AC:

AN:

46622

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.5

PhyloP100

0.92

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.29

MutPred

0.70

Loss of loop (P = 0.0128)

MVP

0.41

MPC

0.26

ClinPred

1.0

GERP RS

3.6

PromoterAI

-0.070

Neutral

(source)

Varity_R

0.83

gMVP

0.77

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over