16-84617577-AGT-GGA

Variant names:

• chr16-84617577-AGT-GGA
• NM_021149.5:c.82_84delACTinsTCC
• COTL1 p.Thr28Ser

Variant summary

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

The NM_021149.5(COTL1):​c.82_84delACTinsTCC​(p.Thr28Ser) 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: 33)
• Consequence: COTL1 NM_021149.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

Genes affected

COTL1 (HGNC:18304): (coactosin like F-actin binding protein 1) This gene encodes one of the numerous actin-binding proteins which regulate the actin cytoskeleton. This protein binds F-actin, and also interacts with 5-lipoxygenase, which is the first committed enzyme in leukotriene biosynthesis. Although this gene has been reported to map to chromosome 17 in the Smith-Magenis syndrome region, the best alignments for this gene are to chromosome 16. The Smith-Magenis syndrome region is the site of two related pseudogenes. [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_021149.5. 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
	COTL1	NM_021149.5	MANE Select	c.82_84delACTinsTCC	p.Thr28Ser	missense	N/A	NP_066972.1	A0A384MTY2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COTL1	ENST00000262428.5	TSL:1 MANE Select	c.82_84delACTinsTCC	p.Thr28Ser	missense	N/A	ENSP00000262428.4	Q14019
	COTL1	ENST00000564057.1	TSL:5	c.-48+259_-48+261delACTinsTCC		intron	N/A	ENSP00000457033.1	H3BT58
	COTL1	ENST00000564662.1	TSL:2	n.497_499delACTinsTCC		non_coding_transcript_exon	Exon 1 of 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		4.6

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: chr16-84651183;