9-128243747-G-T

Variant summary

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

The NM_004408.4(DNM1):c.1671+1402G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,070 control chromosomes in the GnomAD database, including 5,934 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 0.20 (5934 hom., cov: 32)
• Consequence: DNM1 NM_004408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1	NM_004408.4	c.1671+1402G>T		intron_variant		ENST00000372923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1	ENST00000372923.8	c.1671+1402G>T		intron_variant		1	NM_004408.4	A1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30518 AN: 151952 Hom.: 5906 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.201 AC: 30591 AN: 152070 Hom.: 5934 Cov.: 32 AF XY: 0.200 AC XY: 14847 AN XY: 74344

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0605

Gnomad4 OTH AF: 0.179

Alfa AF: 0.0658 Hom.: 171

Bravo AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.065
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10987945; hg19: chr9-131006026;