1-172220749-T-G

Variant names:

• chr1-172220749-T-G
• rs678962
• NM_015569.5:c.1660-32824T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015569.5(DNM3):​c.1660-32824T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,954 control chromosomes in the GnomAD database, including 4,269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4269 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 42 publications found

Genes affected

DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015569.5. 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
	DNM3	NM_015569.5	MANE Select	c.1660-32824T>G		intron	N/A	NP_056384.2
	DNM3	NM_001350204.2		c.1690-32824T>G		intron	N/A	NP_001337133.1	Q9UQ16-1
	DNM3	NM_001136127.3		c.1660-32824T>G		intron	N/A	NP_001129599.1	Q9UQ16-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM3	ENST00000627582.3	TSL:1 MANE Select	c.1660-32824T>G		intron	N/A	ENSP00000486701.1	Q9UQ16-3
	DNM3	ENST00000367731.5	TSL:1	c.1660-32824T>G		intron	N/A	ENSP00000356705.1	Q9UQ16-2
	DNM3	ENST00000485254.3	TSL:1	c.1690-32824T>G		intron	N/A	ENSP00000429165.2	H0YBC6

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35754 AN: 151836 Hom.: 4261 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.222

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 35809 AN: 151954 Hom.: 4269 Cov.: 32 AF XY: 0.232 AC XY: 17223 AN XY: 74280

African (AFR) AF: 0.289 AC: 11990 AN: 41446

American (AMR) AF: 0.219 AC: 3338 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5154

South Asian (SAS) AF: 0.205 AC: 990 AN: 4818

European-Finnish (FIN) AF: 0.187 AC: 1979 AN: 10582

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.215 AC: 14606 AN: 67930

Other (OTH) AF: 0.224 AC: 472 AN: 2108

Alfa AF: 0.225 Hom.: 18859

Bravo AF: 0.243

Asia WGS AF: 0.243 AC: 849 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	15
DANN	Benign	0.58
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs678962; hg19: chr1-172189889;