rs16930313

Positions:

• chr9-128231118-A-G

Variant summary

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

The NM_004408.4(DNM1):​c.1336-2903A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 149,578 control chromosomes in the GnomAD database, including 4,054 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 0.21 (4054 hom., cov: 31)
• Consequence: DNM1 NM_004408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1	NM_004408.4	c.1336-2903A>G		intron_variant		ENST00000372923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1	ENST00000372923.8	c.1336-2903A>G		intron_variant		1	NM_004408.4	A1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 30797 AN: 149476 Hom.: 4043 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.206 AC: 30835 AN: 149578 Hom.: 4054 Cov.: 31 AF XY: 0.208 AC XY: 15154 AN XY: 72852

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.195

Alfa AF: 0.162 Hom.: 625

Bravo AF: 0.209

Asia WGS AF: 0.284 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.3
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16930313; hg19: chr9-130993397;