Variant 20-34534689-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014183.4(DYNLRB1):c.141C>A(p.His47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,605,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

DYNLRB1
NM_014183.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Variant links:

Genes affected

DYNLRB1 (HGNC:15468): (dynein light chain roadblock-type 1) This gene is a member of the roadblock dynein light chain family. The encoded cytoplasmic protein is capable of binding intermediate chain proteins, interacts with transforming growth factor-beta, and has been implicated in the regulation of actin modulating proteins. Upregulation of this gene has been associated with hepatocellular carcinomas, suggesting that this gene may be involved in tumor progression. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 12 and 18. [provided by RefSeq, Aug 2013]

DYNLRB1 links:

ENSG00000289720 (HGNC:):

ENSG00000289720 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2497237).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLRB1	NM_014183.4 linkuse as main transcript	c.141C>A	p.His47Gln	missense_variant	3/4	ENST00000357156.7	NP_054902.1	Q9NP97-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DYNLRB1	ENST00000357156.7 linkuse as main transcript	c.141C>A	p.His47Gln	missense_variant	3/4	1	NM_014183.4	ENSP00000349679.2	Q9NP97-1
ENSG00000289720	ENST00000696979.1 linkuse as main transcript	n.*248C>A		non_coding_transcript_exon_variant	27/28			ENSP00000513014.1
ENSG00000289720	ENST00000696979.1 linkuse as main transcript	n.*248C>A		3_prime_UTR_variant	27/28			ENSP00000513014.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1453406

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

722408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.141C>A (p.H47Q) alteration is located in exon 3 (coding exon 3) of the DYNLRB1 gene. This alteration results from a C to A substitution at nucleotide position 141, causing the histidine (H) at amino acid position 47 to be replaced by a glutamine (Q). 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

0.31

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.089

Eigen_PC

Benign

0.086

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.15

Sift

Benign

0.80

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0020

B;.

Vest4

0.47

MutPred

0.28

Loss of catalytic residue at H47 (P = 0.0602);.;

MVP

0.49

MPC

0.58

ClinPred

0.91

GERP RS

5.1

Varity_R

0.80

gMVP

0.89

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