chr1-66776404-G-A

Variant names:

• chr1-66776404-G-A
• rs3816989
• NM_152665.3:c.336+1G>A

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. Variant has been reported in ClinVar as (no stars).

• 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

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152665.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT5	NM_152665.3	MANE Select	c.336+1G>A		splice_donor intron	N/A	NP_689878.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT5	ENST00000282670.7	TSL:1 MANE Select	c.336+1G>A		splice_donor intron	N/A	ENSP00000282670.2
	DYNLT5	ENST00000528352.1	TSL:1	n.*235+1G>A		splice_donor intron	N/A	ENSP00000436731.1
	DYNLT5	ENST00000909939.1		c.336+1G>A		splice_donor intron	N/A	ENSP00000579998.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17999 AN: 152006 Hom.: 1138 Cov.: 32

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

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.: 31 AF XY: 0.137 AC XY: 98437 AN XY: 716292

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

GnomAD4 genome AF: 0.118 AC: 17998 AN: 152124 Hom.: 1139 Cov.: 32 AF XY: 0.118 AC XY: 8753 AN XY: 74352

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: 45 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8906 AN: 67982

Other (OTH) AF: 0.125 AC: 265 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		8.3
GERP RS		5.9
Mutation Taster		=78/22	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3816989; hg19: chr1-67242087; COSMIC: COSV51075687; COSMIC: COSV51075687;