17-42190733-TC-CT

Variant names:

• chr17-42190733-TC-CT
• NM_032484.5:c.1178_1179delGAinsAG
• GHDC p.Arg393Gln

Variant summary

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

The NM_032484.5(GHDC):​c.1178_1179delGAinsAG​(p.Arg393Gln) 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: GHDC NM_032484.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

Genes affected

GHDC (HGNC:24438): (GH3 domain containing) Predicted to enable acid-amino acid ligase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032484.5. 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
	GHDC	NM_032484.5	MANE Select	c.1178_1179delGAinsAG	p.Arg393Gln	missense	N/A	NP_115873.1	Q8N2G8-1
	GHDC	NM_001142623.2		c.1178_1179delGAinsAG	p.Arg393Gln	missense	N/A	NP_001136095.1	Q8N2G8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHDC	ENST00000587427.6	TSL:1 MANE Select	c.1178_1179delGAinsAG	p.Arg393Gln	missense	N/A	ENSP00000467585.1	Q8N2G8-1
	GHDC	ENST00000301671.12	TSL:2	c.1178_1179delGAinsAG	p.Arg393Gln	missense	N/A	ENSP00000301671.7	Q8N2G8-1
	GHDC	ENST00000853517.1		c.1178_1179delGAinsAG	p.Arg393Gln	missense	N/A	ENSP00000523576.1

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		5.1

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: chr17-40342751;