20-33667682-CG-TA

Variant names:

• chr20-33667682-CG-TA
• NM_001024675.2:c.185_186delCGinsTA
• ACTL10 p.Ala62Val

Variant summary

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

The NM_001024675.2(ACTL10):​c.185_186delCGinsTA​(p.Ala62Val) 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: 33)
• Consequence: ACTL10 NM_001024675.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

Genes affected

ACTL10 (HGNC:16127): (actin like 10) Predicted to be part of dynactin complex. [provided by Alliance of Genome Resources, Apr 2022]

NECAB3 (HGNC:15851): (N-terminal EF-hand calcium binding protein 3) The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein (X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024675.2. 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
	ACTL10	NM_001024675.2	MANE Select	c.185_186delCGinsTA	p.Ala62Val	missense	N/A	NP_001019846.1	Q5JWF8
	NECAB3	NM_031232.4	MANE Select	c.387+1692_387+1693delCGinsTA		intron	N/A	NP_112509.3
	NECAB3	NM_031231.4		c.387+1692_387+1693delCGinsTA		intron	N/A	NP_112508.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTL10	ENST00000677665.1	MANE Select	c.185_186delCGinsTA	p.Ala62Val	missense	N/A	ENSP00000504425.1	Q5JWF8
	NECAB3	ENST00000246190.11	TSL:5 MANE Select	c.387+1692_387+1693delCGinsTA		intron	N/A	ENSP00000246190.6	Q96P71-1
	NECAB3	ENST00000375238.8	TSL:1	c.387+1692_387+1693delCGinsTA		intron	N/A	ENSP00000364386.4	Q96P71-2

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		2.1

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: chr20-32255488;