NM_014320.3:c.253_255delATGinsGTC

Variant names:

• chr6-138405985-ATG-GTC
• NM_014320.3:c.253_255delATGinsGTC
• HEBP2 p.Met85Val

Variant summary

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

The NM_014320.3(HEBP2):​c.253_255delATGinsGTC​(p.Met85Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEBP2 NM_014320.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP2	NM_014320.3	MANE Select	c.253_255delATGinsGTC	p.Met85Val	missense	N/A	NP_055135.1	Q9Y5Z4-1
	HEBP2	NM_001326380.2		c.286_288delATGinsGTC	p.Met96Val	missense	N/A	NP_001313309.1
	HEBP2	NM_001326381.2		c.253_255delATGinsGTC	p.Met85Val	missense	N/A	NP_001313310.1	Q5THN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP2	ENST00000607197.6	TSL:1 MANE Select	c.253_255delATGinsGTC	p.Met85Val	missense	N/A	ENSP00000475750.1	Q9Y5Z4-1
	HEBP2	ENST00000858693.1		c.253_255delATGinsGTC	p.Met85Val	missense	N/A	ENSP00000528752.1
	HEBP2	ENST00000448741.5	TSL:5	c.286_288delATGinsGTC	p.Met96Val	missense	N/A	ENSP00000392101.1	C9IZA0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-138727122;