dbSNP rs201629862: DYNLT1:p.Lys38Ile (chr6-158637851-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006519.4(DYNLT1):c.113A>T(p.Lys38Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K38R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DYNLT1
NM_006519.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.43

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]

DYNLT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT1	NM_006519.4 link	c.113A>T	p.Lys38Ile	missense_variant	Exon 3 of 5	ENST00000367089.8	NP_006510.1	P63172
DYNLT1	NM_001291602.2 link	c.71A>T	p.Lys24Ile	missense_variant	Exon 2 of 4		NP_001278531.1
DYNLT1	NM_001291603.2 link	c.113A>T	p.Lys38Ile	missense_variant	Exon 3 of 5		NP_001278532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNLT1	ENST00000367089.8 link	c.113A>T	p.Lys38Ile	missense_variant	Exon 3 of 5	1	NM_006519.4	ENSP00000356056.3	P63172
DYNLT1	ENST00000367085.3 link	n.143A>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
DYNLT1	ENST00000367088.1 link	n.1514A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.52

MutationAssessor

Pathogenic

3.8

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.017

Polyphen

0.61

Vest4

0.64

MutPred

0.58

Loss of catalytic residue at K38 (P = 0.0045);

MVP

0.80

MPC

0.30

ClinPred

1.0

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over