3-32530496-C-A

Variant names:

• chr3-32530496-C-A
• rs1161762224
• NM_016141.4:c.1105G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016141.4(DYNC1LI1):​c.1105G>T​(p.Ala369Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A369T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYNC1LI1 NM_016141.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1105G>T	p.Ala369Ser	missense	Exon 9 of 13	NP_057225.2	Q9Y6G9
	DYNC1LI1	NM_001329135.2		c.757G>T	p.Ala253Ser	missense	Exon 7 of 11	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.1105G>T	p.Ala369Ser	missense	Exon 9 of 13	ENSP00000273130.4	Q9Y6G9
	DYNC1LI1	ENST00000891300.1		c.1186G>T	p.Ala396Ser	missense	Exon 10 of 14	ENSP00000561359.1
	DYNC1LI1	ENST00000954370.1		c.1096G>T	p.Ala366Ser	missense	Exon 9 of 13	ENSP00000624429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.25
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.044	D
Polyphen		0.99	D
Vest4		0.51
MVP		0.43
MPC		0.61
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.44
gMVP		0.47
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1161762224; hg19: chr3-32571988; COSMIC: COSV56126861;