DNM1 p.Thr111Ser

Variant names:

• chr9-128218677-A-T
• NM_004408.4:c.331A>T
• DNM1 p.Thr111Ser

Your query was ambiguous. Multiple possible variants found:

• chr9-128218677-A-T
• chr9-128218678-C-G
• chr9-128218677-ACC-TCT
• chr9-128218677-ACC-TCA
• chr9-128218677-ACC-TCG
• chr9-128218678-CC-GT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004408.4(DNM1):​c.331A>T​(p.Thr111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNM1 NM_004408.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 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, AR 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084498316).

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.331A>T	p.Thr111Ser	missense	Exon 3 of 22	NP_004399.2	Q05193-1
	DNM1	NM_001374269.1		c.331A>T	p.Thr111Ser	missense	Exon 3 of 22	NP_001361198.1	A0A994J7J4
	DNM1	NM_001288739.2		c.331A>T	p.Thr111Ser	missense	Exon 3 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.331A>T	p.Thr111Ser	missense	Exon 3 of 22	ENSP00000362014.4	Q05193-1
	DNM1	ENST00000486160.3	TSL:1	c.331A>T	p.Thr111Ser	missense	Exon 3 of 22	ENSP00000420045.1	Q05193-2
	DNM1	ENST00000634267.2	TSL:5	c.331A>T	p.Thr111Ser	missense	Exon 3 of 22	ENSP00000489096.1	A0A0U1RQP1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.084	T
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Benign	-0.99	N
PhyloP100		2.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.33
Mutation Taster		=95/5	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-130980956;