22-17138585-GCC-ACA

Variant names:

• chr22-17138585-GCC-ACA
• NM_033070.3:c.898_900delGGCinsTGT
• HDHD5 p.Gly300Cys

Variant summary

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

The NM_033070.3(HDHD5):​c.898_900delGGCinsTGT​(p.Gly300Cys) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G300S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDHD5 NM_033070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44
• Publications: 0 publications found

Genes affected

HDHD5 (HGNC:1843): (haloacid dehalogenase like hydrolase domain containing 5) Predicted to be involved in glycerophospholipid biosynthetic process. Predicted to be active in mitochondrion. [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_033070.3. 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
	HDHD5	NM_033070.3	MANE Select	c.898_900delGGCinsTGT	p.Gly300Cys	missense	N/A	NP_149061.1	Q9BXW7-1
	HDHD5	NM_017829.6		c.808_810delGGCinsTGT	p.Gly270Cys	missense	N/A	NP_060299.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD5	ENST00000336737.8	TSL:1 MANE Select	c.898_900delGGCinsTGT	p.Gly300Cys	missense	N/A	ENSP00000337358.4	Q9BXW7-1
	HDHD5	ENST00000155674.9	TSL:1	c.808_810delGGCinsTGT	p.Gly270Cys	missense	N/A	ENSP00000155674.5	Q9BXW7-2
	HDHD5	ENST00000477157.5	TSL:1	n.2741_2743delGGCinsTGT		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.4

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: chr22-17619475;