Genetic Variant DYNLT1:p.Ser92Asn (chr6-158636894-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006519.4(DYNLT1):c.275G>A(p.Ser92Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00024 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

DYNLT1
NM_006519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27791268).

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT1	NM_006519.4 link	c.275G>A	p.Ser92Asn	missense_variant	Exon 5 of 5	ENST00000367089.8	NP_006510.1	P63172
DYNLT1	NM_001291602.2 link	c.233G>A	p.Ser78Asn	missense_variant	Exon 4 of 4		NP_001278531.1
DYNLT1	NM_001291603.2 link	c.*6G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001278532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNLT1	ENST00000367089.8 link	c.275G>A	p.Ser92Asn	missense_variant	Exon 5 of 5	1	NM_006519.4	ENSP00000356056.3		P63172
DYNLT1	ENST00000367088.1 link	n.2471G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000220

AC:

AN:

250074

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000451

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000235

AC:

344

AN:

1461222

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000302

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000289

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000488

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000713

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.275G>A (p.S92N) alteration is located in exon 5 (coding exon 5) of the DYNLT1 gene. This alteration results from a G to A substitution at nucleotide position 275, causing the serine (S) at amino acid position 92 to be replaced by an asparagine (N). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

M_CAP

Benign

0.010

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.15

Sift

Benign

0.096

Sift4G

Benign

0.18

Polyphen

0.62

Vest4

0.23

MVP

0.75

MPC

0.045

ClinPred

0.19

GERP RS

5.1

Varity_R

0.67

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over