Genetic Variant DYNLT5:c.336+1G>A (chr1-66776404-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_152665.3(DYNLT5):c.336+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,596,222 control chromosomes in the GnomAD database, including 14,913 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1139 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13774 hom. )

Consequence

DYNLT5
NM_152665.3 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.33

Publications

28 publications found

Variant links:

Genes affected

DYNLT5 (HGNC:26882): (dynein light chain Tctex-type family member 5) Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DYNLT5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT5	NM_152665.3 link	c.336+1G>A		splice_donor_variant, intron_variant	Intron 4 of 4	ENST00000282670.7	NP_689878.2	Q8N7M0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNLT5	ENST00000282670.7 link	c.336+1G>A	splice_donor_variant, intron_variant	Intron 4 of 4	1	NM_152665.3	ENSP00000282670.2	Q8N7M0-1
DYNLT5	ENST00000528352.1 link	n.*235+1G>A	splice_donor_variant, intron_variant	Intron 6 of 6	1		ENSP00000436731.1	E9PI84
DYNLT5	ENST00000489510.1 link	n.249+1G>A	splice_donor_variant, intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17999

AN:

152006

Hom.:

1138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.136

AC:

33160

AN:

244602

AF XY:

0.142

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.0873

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.137

GnomAD4 exome

AF:

0.136

AC:

195787

AN:

1444098

Hom.:

13774

Cov.:

AF XY:

0.137

AC XY:

98437

AN XY:

716292

show subpopulations

African (AFR)

AF:

0.0770

AC:

2544

AN:

33058

American (AMR)

AF:

0.0894

AC:

3880

AN:

43416

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4715

AN:

25708

East Asian (EAS)

AF:

0.149

AC:

5825

AN:

39204

South Asian (SAS)

AF:

0.169

AC:

14010

AN:

82880

European-Finnish (FIN)

AF:

0.134

AC:

7100

AN:

53056

Middle Eastern (MID)

AF:

0.167

AC:

951

AN:

5688

European-Non Finnish (NFE)

AF:

0.135

AC:

148512

AN:

1101342

Other (OTH)

AF:

0.138

AC:

8250

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

7690

15380

23070

30760

38450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.118

AC:

17998

AN:

152124

Hom.:

1139

Cov.:

AF XY:

0.118

AC XY:

8753

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0819

AC:

3401

AN:

41504

American (AMR)

AF:

0.112

AC:

1713

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

609

AN:

3468

East Asian (EAS)

AF:

0.137

AC:

709

AN:

5182

South Asian (SAS)

AF:

0.160

AC:

773

AN:

4824

European-Finnish (FIN)

AF:

0.134

AC:

1418

AN:

10568

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8906

AN:

67982

Other (OTH)

AF:

0.125

AC:

265

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

845

1690

2536

3381

4226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.131

Hom.:

3725

Bravo

AF:

0.117

TwinsUK

AF:

0.133

AC:

495

ALSPAC

AF:

0.121

AC:

468

ESP6500AA

AF:

0.0831

AC:

366

ESP6500EA

AF:

0.138

AC:

1187

ExAC

AF:

0.137

AC:

16572

Asia WGS

AF:

0.128

AC:

446

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

0.99

PhyloP100

8.3

GERP RS

5.9

Mutation Taster

=78/22

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.99

Position offset: -1

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

Publications

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chr1-66776404-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over