chr6-158641327-C-A

Variant summary

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

The NM_006519.4(DYNLT1):​c.61G>T​(p.Val21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)

Consequence

DYNLT1
NM_006519.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77
Variant links:
Genes affected
DYNLT1 (HGNC:11697): (dynein light chain Tctex-type 1) This gene encodes a component of the motor complex, cytoplasmic dynein, which transports cellular cargo along microtubules in the cell. The encoded protein regulates the length of primary cilia which are sensory organelles found on the surface of cells. The protein encoded by this gene interacts with viral proteins, like the minor capsid protein L2 of human papillomavirus, and is required for dynein-mediated delivery of the viral nucleic acid to the host nucleus. This protein interacts with oncogenic nucleoporins to disrupt gene regulation and cause leukemic transformation. Pseudogenes of this gene are present on chromosomes 4 and 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

Genome browser will be placed here

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=0.31363273).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYNLT1NM_006519.4 linkc.61G>T p.Val21Leu missense_variant Exon 2 of 5 ENST00000367089.8 NP_006510.1 P63172
DYNLT1NM_001291603.2 linkc.61G>T p.Val21Leu missense_variant Exon 2 of 5 NP_001278532.1
DYNLT1NM_001291602.2 linkc.27+3355G>T intron_variant Intron 1 of 3 NP_001278531.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNLT1ENST00000367089.8 linkc.61G>T p.Val21Leu missense_variant Exon 2 of 5 1 NM_006519.4 ENSP00000356056.3 P63172
DYNLT1ENST00000367085.3 linkn.91G>T non_coding_transcript_exon_variant Exon 2 of 3 2
DYNLT1ENST00000367088.1 linkn.1462G>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 22, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.61G>T (p.V21L) alteration is located in exon 2 (coding exon 2) of the DYNLT1 gene. This alteration results from a G to T substitution at nucleotide position 61, causing the valine (V) at amino acid position 21 to be replaced by a leucine (L). 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
Uncertain
0.52
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.091
Eigen_PC
Benign
0.024
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.10
Sift
Benign
0.064
T
Sift4G
Benign
0.19
T
Polyphen
0.013
B
Vest4
0.45
MutPred
0.71
Loss of methylation at K22 (P = 0.0425);
MVP
0.64
MPC
0.052
ClinPred
0.78
D
GERP RS
3.4
Varity_R
0.21
gMVP
0.48

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: chr6-159062359; API