9-137564450-GT-AC

Variant names:

• chr9-137564450-GT-AC
• NM_138778.5:c.932_933delACinsGT
• DPH7 p.Asn311Ser

Variant summary

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

The NM_138778.5(DPH7):​c.932_933delACinsGT​(p.Asn311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: DPH7 NM_138778.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

Genes affected

DPH7 (HGNC:25199): (diphthamide biosynthesis 7) Diphthamide is a post-translationally modified histidine residue present in elongation factor 2, and is the target of diphtheria toxin. This gene encodes a protein that contains a WD-40 domain, and is thought to be involved in diphthamide biosynthesis. A similar protein in yeast functions as a methylesterase, converting methylated diphthine to diphthine, which can then undergo amidation to produce diphthamide. [provided by RefSeq, Oct 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138778.5. 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
	DPH7	NM_138778.5	MANE Select	c.932_933delACinsGT	p.Asn311Ser	missense	N/A	NP_620133.1	Q9BTV6
	DPH7	NM_001346370.2		c.866_867delACinsGT	p.Asn289Ser	missense	N/A	NP_001333299.1
	DPH7	NM_001346371.2		c.932_933delACinsGT	p.Asn311Ser	missense	N/A	NP_001333300.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPH7	ENST00000277540.7	TSL:1 MANE Select	c.932_933delACinsGT	p.Asn311Ser	missense	N/A	ENSP00000277540.2	Q9BTV6
	DPH7	ENST00000467243.5	TSL:1	n.549_550delACinsGT		non_coding_transcript_exon	Exon 1 of 2
	DPH7	ENST00000872889.1		c.866_867delACinsGT	p.Asn289Ser	missense	N/A	ENSP00000542948.1

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		3.3

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: chr9-140458902;