chr3-32530496-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

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

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
DYNC1LI1	NM_016141.4	c.1105G>A	p.Ala369Thr	missense_variant	Exon 9 of 13	ENST00000273130.9	NP_057225.2
DYNC1LI1	NM_001329135.2	c.757G>A	p.Ala253Thr	missense_variant	Exon 7 of 11		NP_001316064.1
DYNC1LI1	XM_047448246.1	c.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
DYNC1LI1	ENST00000273130.9	c.1105G>A	p.Ala369Thr	missense_variant	Exon 9 of 13	1	NM_016141.4	ENSP00000273130.4
DYNC1LI1	ENST00000432458.6	c.757G>A	p.Ala253Thr	missense_variant	Exon 7 of 11	2		ENSP00000407279.2
DYNC1LI1	ENST00000472985.1	n.535G>A		non_coding_transcript_exon_variant	Exon 4 of 6	3
DYNC1LI1	ENST00000481915.5	n.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

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;