1-171980610-T-C

Position:

• chr1-171980610-T-C

Variant summary

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

The NM_015569.5(DNM3):​c.236-7046T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,982 control chromosomes in the GnomAD database, including 46,412 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 0.78 (46412 hom., cov: 30)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM3	NM_015569.5	c.236-7046T>C		intron_variant		ENST00000627582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM3	ENST00000627582.3	c.236-7046T>C		intron_variant		1	NM_015569.5	A1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118607 AN: 151864 Hom.: 46363 Cov.: 30

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.781 AC: 118713 AN: 151982 Hom.: 46412 Cov.: 30 AF XY: 0.780 AC XY: 57908 AN XY: 74254

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.804

Alfa AF: 0.787 Hom.: 9054

Bravo AF: 0.781

Asia WGS AF: 0.796 AC: 2766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10914144; hg19: chr1-171949750;