rs371426966

Positions:

• chr9-128239524-TC-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_004408.4(DNM1):​c.1493+14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,609,628 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00062 (4 hom.)
• Consequence: DNM1 NM_004408.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.57

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.

• BP6: Variant 9-128239524-TC-T is Benign according to our data. Variant chr9-128239524-TC-T is described in ClinVar as [Benign]. Clinvar id is 476061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM1	NM_004408.4	c.1493+14del		intron_variant		ENST00000372923.8	NP_004399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8	c.1493+14del		intron_variant		1	NM_004408.4	ENSP00000362014	A1

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 62 AN: 149584 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000671

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00443

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000429

Gnomad OTH AF: 0.000973

GnomAD3 exomes AF: 0.00102 AC: 255 AN: 251058 Hom.: 1 AF XY: 0.00112 AC XY: 152 AN XY: 135686

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00485

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.000616 AC: 899 AN: 1459934 Hom.: 4 Cov.: 32 AF XY: 0.000716 AC XY: 520 AN XY: 726232

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00485

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000269

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.000414 AC: 62 AN: 149694 Hom.: 0 Cov.: 31 AF XY: 0.000439 AC XY: 32 AN XY: 72974

Gnomad4 AFR AF: 0.0000247

Gnomad4 AMR AF: 0.0000671

Gnomad4 ASJ AF: 0.00233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00443

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000429

Gnomad4 OTH AF: 0.000962

Alfa AF: 0.000781 Hom.: 0

Bravo AF: 0.000359

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2016	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	DNM1: BS1, BS2 -

Developmental and epileptic encephalopathy, 31A Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs371426966; hg19: chr9-131001803;