rs11771

Variant names:

• chrX-37841795-G-A
• rs11771
• NM_006520.3:c.183C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006520.3(DYNLT3):​c.183C>T​(p.Ala61Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,169,836 control chromosomes in the GnomAD database, including 19,938 homozygotes. There are 69,861 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (5606 hom., 9496 hem., cov: 22)
  • Exomes 𝑓: 0.18 (14332 hom. 60365 hem.)
• Consequence: DYNLT3 NM_006520.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.608

Genes affected

DYNLT3 (HGNC:11694): (dynein light chain Tctex-type 3) This gene encodes a member of a subclass of dynein light chains. The encoded protein homodimerizes and forms the light chain component of the cytoplasmic dynein motor protein complex. This protein may be important for binding dynein to specific cargos including the spindle checkpoint protein BUB3. This protein may also function independently of dynein as a transcriptional modulator. Pseudogenes of this gene are found on chromosomes 2 and 20.[provided by RefSeq, Mar 2010]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant X-37841795-G-A is Benign according to our data. Variant chrX-37841795-G-A is described in ClinVar as [Benign]. Clinvar id is 402816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-37841795-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.608 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT3	NM_006520.3	c.183C>T	p.Ala61Ala	synonymous_variant	Exon 3 of 5	ENST00000378578.9	NP_006511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNLT3	ENST00000378578.9	c.183C>T	p.Ala61Ala	synonymous_variant	Exon 3 of 5	1	NM_006520.3	ENSP00000367841.4
ENSG00000250349	ENST00000465127.1	c.171+415795G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
DYNLT3	ENST00000378581.7	c.183C>T	p.Ala61Ala	synonymous_variant	Exon 3 of 6	2		ENSP00000367844.3
DYNLT3	ENST00000432389.2	c.201C>T	p.Ala67Ala	synonymous_variant	Exon 3 of 5	5		ENSP00000402695.2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 33795 AN: 109893 Hom.: 5607 Cov.: 22 AF XY: 0.294 AC XY: 9461 AN XY: 32197

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.218 AC: 38439 AN: 176427 Hom.: 4048 AF XY: 0.202 AC XY: 12413 AN XY: 61335

Gnomad AFR exome AF: 0.660

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.242

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.178 AC: 188160 AN: 1059891 Hom.: 14332 Cov.: 29 AF XY: 0.178 AC XY: 60365 AN XY: 338771

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.308 AC: 33827 AN: 109945 Hom.: 5606 Cov.: 22 AF XY: 0.294 AC XY: 9496 AN XY: 32259

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.260

Alfa AF: 0.231 Hom.: 2182

Bravo AF: 0.327

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.1
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs11771; hg19: chrX-37701048; COSMIC: COSV66079168;