rs143834670

Variant names:

• chr9-128219113-C-G
• rs143834670
• NM_004408.4:c.450C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-128219113-C-G
• chr9-128219113-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_004408.4(DNM1):​c.450C>G​(p.Pro150Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: DNM1 NM_004408.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.12
• Publications: 1 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: AR, AD Classification: DEFINITIVE, MODERATE 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-128219113-C-G is Benign according to our data. Variant chr9-128219113-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 388987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.12 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	NM_004408.4	MANE Select	c.450C>G	p.Pro150Pro	synonymous	Exon 4 of 22	NP_004399.2	Q05193-1
	DNM1	NM_001374269.1		c.450C>G	p.Pro150Pro	synonymous	Exon 4 of 22	NP_001361198.1	A0A994J7J4
	DNM1	NM_001288739.2		c.450C>G	p.Pro150Pro	synonymous	Exon 4 of 22	NP_001275668.1	Q05193-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	ENST00000372923.8	TSL:1 MANE Select	c.450C>G	p.Pro150Pro	synonymous	Exon 4 of 22	ENSP00000362014.4	Q05193-1
	DNM1	ENST00000486160.3	TSL:1	c.450C>G	p.Pro150Pro	synonymous	Exon 4 of 22	ENSP00000420045.1	Q05193-2
	DNM1	ENST00000634267.2	TSL:5	c.450C>G	p.Pro150Pro	synonymous	Exon 4 of 22	ENSP00000489096.1	A0A0U1RQP1

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 133 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000919 AC: 231 AN: 251450 AF XY: 0.000876

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00168 AC: 2458 AN: 1461846 Hom.: 1 Cov.: 32 AF XY: 0.00159 AC XY: 1153 AN XY: 727222

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00213 AC: 2364 AN: 1112008

Other (OTH) AF: 0.000944 AC: 57 AN: 60396

GnomAD4 genome AF: 0.000873 AC: 133 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000631 AC XY: 47 AN XY: 74476

African (AFR) AF: 0.000337 AC: 14 AN: 41576

American (AMR) AF: 0.000261 AC: 4 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.000854

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy, 31A (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		-4.1
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs143834670; hg19: chr9-130981392;