1-17823069-GGC-TCA

Variant names:

• chr1-17823069-GGC-TCA
• NM_030812.3:c.61_63delGGCinsTCA
• ACTL8 p.Gly21Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_030812.3(ACTL8):​c.61_63delGGCinsTCA​(p.Gly21Ser) variant causes a missense change involving the alteration of a 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: 33)
• Consequence: ACTL8 NM_030812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77
• Publications: 0 publications found

Genes affected

ACTL8 (HGNC:24018): (actin like 8) Involved in epithelial cell differentiation. Predicted to be located in cytoplasm. Predicted to be part of dynactin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030812.3. 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
	ACTL8	NM_030812.3	MANE Select	c.61_63delGGCinsTCA	p.Gly21Ser	missense	N/A	NP_110439.2	Q9H568

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTL8	ENST00000375406.2	TSL:1 MANE Select	c.61_63delGGCinsTCA	p.Gly21Ser	missense	N/A	ENSP00000364555.1	Q9H568
	ACTL8	ENST00000617065.1	TSL:2	c.61_63delGGCinsTCA	p.Gly21Ser	missense	N/A	ENSP00000481590.1	Q9H568
	ACTL8	ENST00000922969.1		c.61_63delGGCinsTCA	p.Gly21Ser	missense	N/A	ENSP00000593028.1

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		7.8

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: chr1-18149564;