9-128224244-C-T

Variant names:

• chr9-128224244-C-T
• rs41306488
• NM_004408.4:c.1197-7C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_004408.4(DNM1):​c.1197-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,612,622 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: DNM1 NM_004408.4 splice_region, intron
• Scores: Splicing: ADA: 0.002558
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 9-128224244-C-T is Benign according to our data. Variant chr9-128224244-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1	NM_004408.4	c.1197-7C>T		splice_region_variant, intron_variant	Intron 9 of 21	ENST00000372923.8	NP_004399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8	c.1197-7C>T		splice_region_variant, intron_variant	Intron 9 of 21	1	NM_004408.4	ENSP00000362014.4
DNM1	ENST00000634267.2	c.1197-7C>T		splice_region_variant, intron_variant	Intron 9 of 21	5		ENSP00000489096.1

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152232 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00237 AC: 592 AN: 250250 Hom.: 1 AF XY: 0.00230 AC XY: 311 AN XY: 135240

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00260

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000493

Gnomad FIN exome AF: 0.00412

Gnomad NFE exome AF: 0.00352

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00300 AC: 4376 AN: 1460272 Hom.: 13 Cov.: 31 AF XY: 0.00300 AC XY: 2178 AN XY: 726328

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00295

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000407

Gnomad4 FIN exome AF: 0.00453

Gnomad4 NFE exome AF: 0.00338

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152350 Hom.: 2 Cov.: 32 AF XY: 0.00252 AC XY: 188 AN XY: 74510

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00461

Gnomad4 NFE AF: 0.00373

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00237 Hom.: 0

Bravo AF: 0.00227

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNM1: BP4, BS2 -

Developmental and epileptic encephalopathy, 31A Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.93
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0026
dbscSNV1_RF	Benign	0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs41306488; hg19: chr9-130986523;