chr9-128214278-C-T

Position:

• chr9-128214278-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004408.4(DNM1):​c.162-3953C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,916 control chromosomes in the GnomAD database, including 30,450 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 0.63 (30450 hom., cov: 31)
• Consequence: DNM1 NM_004408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1	NM_004408.4	c.162-3953C>T		intron_variant		ENST00000372923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1	ENST00000372923.8	c.162-3953C>T		intron_variant		1	NM_004408.4	A1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95941 AN: 151798 Hom.: 30427 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.632 AC: 96007 AN: 151916 Hom.: 30450 Cov.: 31 AF XY: 0.631 AC XY: 46824 AN XY: 74258

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.635

Alfa AF: 0.642 Hom.: 59042

Bravo AF: 0.641

Asia WGS AF: 0.699 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.98
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2502731; hg19: chr9-130976557;