chr9-128243747-G-T

Variant names:

• chr9-128243747-G-T
• rs10987945
• NM_004408.4:c.1671+1402G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

DNM1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 31A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• developmental and epileptic encephalopathy, 31B

  Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Lennox-Gastaut syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004408.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	NM_004408.4	MANE Select	c.1671+1402G>T		intron	N/A	NP_004399.2
	DNM1	NM_001374269.1		c.1671+1402G>T		intron	N/A	NP_001361198.1
	DNM1	NM_001288739.2		c.1671+1402G>T		intron	N/A	NP_001275668.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	ENST00000372923.8	TSL:1 MANE Select	c.1671+1402G>T		intron	N/A	ENSP00000362014.4
	DNM1	ENST00000486160.3	TSL:1	c.1671+1402G>T		intron	N/A	ENSP00000420045.1
	DNM1	ENST00000634267.2	TSL:5	c.1671+1402G>T		intron	N/A	ENSP00000489096.1

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

African (AFR) AF: 0.498 AC: 20624 AN: 41418

American (AMR) AF: 0.154 AC: 2358 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1492 AN: 5154

South Asian (SAS) AF: 0.132 AC: 637 AN: 4820

European-Finnish (FIN) AF: 0.0587 AC: 623 AN: 10616

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4110 AN: 67976

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.0817 Hom.: 262

Bravo AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.065
DANN	Benign	0.66
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10987945; hg19: chr9-131006026;