3-32530496-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016141.4(DYNC1LI1):​c.1105G>A​(p.Ala369Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DYNC1LI1
NM_016141.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36476496).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYNC1LI1NM_016141.4 linkc.1105G>A p.Ala369Thr missense_variant Exon 9 of 13 ENST00000273130.9 NP_057225.2 Q9Y6G9
DYNC1LI1NM_001329135.2 linkc.757G>A p.Ala253Thr missense_variant Exon 7 of 11 NP_001316064.1 E9PHI6
DYNC1LI1XM_047448246.1 linkc.667G>A p.Ala223Thr missense_variant Exon 8 of 12 XP_047304202.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNC1LI1ENST00000273130.9 linkc.1105G>A p.Ala369Thr missense_variant Exon 9 of 13 1 NM_016141.4 ENSP00000273130.4 Q9Y6G9
DYNC1LI1ENST00000432458.6 linkc.757G>A p.Ala253Thr missense_variant Exon 7 of 11 2 ENSP00000407279.2 E9PHI6
DYNC1LI1ENST00000472985.1 linkn.535G>A non_coding_transcript_exon_variant Exon 4 of 6 3
DYNC1LI1ENST00000481915.5 linkn.3493G>A non_coding_transcript_exon_variant Exon 8 of 11 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1105G>A (p.A369T) alteration is located in exon 9 (coding exon 9) of the DYNC1LI1 gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the alanine (A) at amino acid position 369 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Benign
0.17
Sift
Benign
0.15
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.79
P;D
Vest4
0.32
MutPred
0.59
Loss of sheet (P = 0.0084);.;
MVP
0.48
MPC
0.46
ClinPred
0.98
D
GERP RS
5.1
Varity_R
0.37
gMVP
0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-32571988; API