3-32537012-C-G

Variant names:

• chr3-32537012-C-G
• rs1478050321
• NM_016141.4:c.831G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016141.4(DYNC1LI1):​c.831G>C​(p.Gln277His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q277R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: DYNC1LI1 NM_016141.4 missense, splice_region
• Scores: Splicing: ADA: 0.003170
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.612
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17027378).

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.831G>C	p.Gln277His	missense splice_region	Exon 6 of 13	NP_057225.2	Q9Y6G9
	DYNC1LI1	NM_001329135.2		c.483G>C	p.Gln161His	missense splice_region	Exon 4 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.831G>C	p.Gln277His	missense splice_region	Exon 6 of 13	ENSP00000273130.4	Q9Y6G9
	DYNC1LI1	ENST00000891300.1		c.912G>C	p.Gln304His	missense splice_region	Exon 7 of 14	ENSP00000561359.1
	DYNC1LI1	ENST00000954370.1		c.831G>C	p.Gln277His	missense splice_region	Exon 6 of 13	ENSP00000624429.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000423 AC: 1 AN: 236236 AF XY: 0.00000779

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000287 AC: 4 AN: 1395804 Hom.: 0 Cov.: 24 AF XY: 0.00000287 AC XY: 2 AN XY: 697490

African (AFR) AF: 0.00 AC: 0 AN: 31514

American (AMR) AF: 0.00 AC: 0 AN: 39168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25510

East Asian (EAS) AF: 0.00 AC: 0 AN: 38400

South Asian (SAS) AF: 0.00 AC: 0 AN: 81610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00000376 AC: 4 AN: 1062654

Other (OTH) AF: 0.00 AC: 0 AN: 58056

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.61
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.014	D
Polyphen		0.068	B
Vest4		0.20
MutPred		0.68		Gain of sheet (P = 0.0344)
MVP		0.46
MPC		0.22
ClinPred		0.52	D
GERP RS		2.9
Varity_R		0.18
gMVP		0.59
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0032
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: rs1478050321; hg19: chr3-32578504;