rs4072117

chr1-172239731-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015569.5(DNM3):c.1660-13842T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,514 control chromosomes in the GnomAD database, including 2,426 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 0.16 (2426 hom., cov: 30)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM3	NM_015569.5	c.1660-13842T>C		intron_variant		ENST00000627582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM3	ENST00000627582.3	c.1660-13842T>C		intron_variant		1	NM_015569.5	A1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24935 AN: 151404 Hom.: 2422 Cov.: 30

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.165 AC: 24958 AN: 151514 Hom.: 2426 Cov.: 30 AF XY: 0.163 AC XY: 12043 AN XY: 73958

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.176

Alfa AF: 0.172 Hom.: 495

Bravo AF: 0.164

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.99
Dann	Benign	0.69

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: rs4072117; hg19: chr1-172208871;