Genetic Variant NM_004408.4:c.36G>T (chr9-128203506-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004408.4(DNM1):c.36G>T(p.Leu12Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L12L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNM1
NM_004408.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.61

Publications

0 publications found

Variant links:

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 links:

CIZ1 (HGNC:16744): (CDKN1A interacting zinc finger protein 1) The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CIZ1 Gene-Disease associations (from GenCC):

dystonia 23
Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp
inherited dystonia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CIZ1 links:

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new If you want to explore the variant's impact on the transcript NM_004408.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNM1	NM_004408.4	MANE Select	c.36G>T	p.Leu12Leu	synonymous	Exon 1 of 22	NP_004399.2	Q05193-1
DNM1	NM_001374269.1		c.36G>T	p.Leu12Leu	synonymous	Exon 1 of 22	NP_001361198.1	A0A994J7J4
DNM1	NM_001288739.2		c.36G>T	p.Leu12Leu	synonymous	Exon 1 of 22	NP_001275668.1	Q05193-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNM1	ENST00000372923.8	TSL:1 MANE Select	c.36G>T	p.Leu12Leu	synonymous	Exon 1 of 22	ENSP00000362014.4	Q05193-1
DNM1	ENST00000486160.3	TSL:1	c.36G>T	p.Leu12Leu	synonymous	Exon 1 of 22	ENSP00000420045.1	Q05193-2
DNM1	ENST00000634267.2	TSL:5	c.36G>T	p.Leu12Leu	synonymous	Exon 1 of 22	ENSP00000489096.1	A0A0U1RQP1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1385846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687940

African (AFR)

AF:

0.00

AC:

AN:

28586

American (AMR)

AF:

0.00

AC:

AN:

35030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23944

East Asian (EAS)

AF:

0.00

AC:

AN:

31330

South Asian (SAS)

AF:

0.00

AC:

AN:

78324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077692

Other (OTH)

AF:

0.00

AC:

AN:

56880

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

5.6

PromoterAI

-0.093

Neutral

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over