1-172230433-T-G

Variant names:

• chr1-172230433-T-G
• rs479336
• NM_015569.5:c.1660-23140T>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.1660-23140T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,976 control chromosomes in the GnomAD database, including 11,908 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 0.36 (11908 hom., cov: 31)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 34 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1660-23140T>G		intron_variant	Intron 14 of 20	ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1660-23140T>G		intron_variant	Intron 14 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54955 AN: 151858 Hom.: 11853 Cov.: 31

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.362 AC: 55083 AN: 151976 Hom.: 11908 Cov.: 31 AF XY: 0.359 AC XY: 26641 AN XY: 74276

African (AFR) AF: 0.613 AC: 25416 AN: 41440

American (AMR) AF: 0.287 AC: 4377 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1775 AN: 5164

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4818

European-Finnish (FIN) AF: 0.255 AC: 2696 AN: 10572

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17391 AN: 67944

Other (OTH) AF: 0.344 AC: 723 AN: 2104

Alfa AF: 0.290 Hom.: 22791

Bravo AF: 0.377

Asia WGS AF: 0.361 AC: 1254 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.76
DANN	Benign	0.69
PhyloP100		-0.64
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: rs479336; hg19: chr1-172199573;