rs13285411

Positions:

• chr9-128235589-C-A

Variant summary

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

The ENST00000372923.8(DNM1):​c.1422+1482C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,098 control chromosomes in the GnomAD database, including 2,334 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 (2334 hom., cov: 32)
• Consequence: DNM1 ENST00000372923.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM1	NM_004408.4	c.1422+1482C>A		intron_variant		ENST00000372923.8	NP_004399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8	c.1422+1482C>A		intron_variant		1	NM_004408.4	ENSP00000362014	A1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24864 AN: 151980 Hom.: 2331 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.164 AC: 24883 AN: 152098 Hom.: 2334 Cov.: 32 AF XY: 0.166 AC XY: 12337 AN XY: 74362

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.163

Alfa AF: 0.134 Hom.: 1917

Bravo AF: 0.161

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13285411; hg19: chr9-130997868;