20-34534689-C-G

Variant names:

• chr20-34534689-C-G
• rs11537532
• NM_014183.4:c.141C>G

Variant summary

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

The NM_014183.4(DYNLRB1):​c.141C>G​(p.His47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DYNLRB1 NM_014183.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03
• Publications: 0 publications found

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]

ENSG00000289720 (HGNC:):

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=0.25432143).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014183.4. 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
	DYNLRB1	NM_014183.4	MANE Select	c.141C>G	p.His47Gln	missense	Exon 3 of 4	NP_054902.1	Q9NP97-1
	DYNLRB1	NM_001319157.2		c.141C>G	p.His47Gln	missense	Exon 3 of 3	NP_001306086.1	B4DFR2
	DYNLRB1	NM_001382365.1		c.141C>G	p.His47Gln	missense	Exon 4 of 5	NP_001369294.1	Q9NP97-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLRB1	ENST00000357156.7	TSL:1 MANE Select	c.141C>G	p.His47Gln	missense	Exon 3 of 4	ENSP00000349679.2	Q9NP97-1
	ENSG00000289720	ENST00000696979.1		n.*248C>G		non_coding_transcript_exon	Exon 27 of 28	ENSP00000513014.1
	ENSG00000289720	ENST00000696979.1		n.*248C>G		3_prime_UTR	Exon 27 of 28	ENSP00000513014.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453406 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722408

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25334

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 84634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107312

Other (OTH) AF: 0.00 AC: 0 AN: 60058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Benign	0.81
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.089
Eigen_PC	Benign	0.086
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.15
Sift	Benign	0.80	T
Sift4G	Benign	0.74	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	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.89
Mutation Taster		=20/80	disease causing

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

Other links and lift over

dbSNP: rs11537532; hg19: chr20-33122493;