3-32530494-TGC-AGT

Variant names:

• chr3-32530494-TGC-AGT
• NM_016141.4:c.1105_1107delGCAinsACT
• DYNC1LI1 p.Ala369Thr

Variant summary

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

The NM_016141.4(DYNC1LI1):​c.1105_1107delGCAinsACT​(p.Ala369Thr) 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: 32)
• Consequence: DYNC1LI1 NM_016141.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94
• Publications: 0 publications found

Genes affected

DYNC1LI1 (HGNC:18745): (dynein cytoplasmic 1 light intermediate chain 1) The protein encoded by this gene belongs to light intermediate subunit family, whose members are components of the multiprotein cytoplasmic dynein complex, which is involved in intracellular trafficking and chromosome segregation during mitosis. The protein plays a role in moving the spindle assembly checkpoint (SAC) from kinetochores to spindle poles. The protein may also mediate binding to other cargo molecules to facilitate intracellular vesicle trafficking. [provided by RefSeq, Jul 2016]

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_016141.4. 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
	DYNC1LI1	NM_016141.4	MANE Select	c.1105_1107delGCAinsACT	p.Ala369Thr	missense	N/A	NP_057225.2	Q9Y6G9
	DYNC1LI1	NM_001329135.2		c.757_759delGCAinsACT	p.Ala253Thr	missense	N/A	NP_001316064.1	E9PHI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1LI1	ENST00000273130.9	TSL:1 MANE Select	c.1105_1107delGCAinsACT	p.Ala369Thr	missense	N/A	ENSP00000273130.4	Q9Y6G9
	DYNC1LI1	ENST00000891300.1		c.1186_1188delGCAinsACT	p.Ala396Thr	missense	N/A	ENSP00000561359.1
	DYNC1LI1	ENST00000954370.1		c.1096_1098delGCAinsACT	p.Ala366Thr	missense	N/A	ENSP00000624429.1

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		9.9

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: chr3-32571986;