1-172385992-G-A

Position:

• chr1-172385992-G-A

Variant summary

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

The NM_015569.5(DNM3):​c.2059-1141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,142 control chromosomes in the GnomAD database, including 40,542 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 0.70 (40542 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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]

PIGC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM3	NM_015569.5	c.2059-1141G>A		intron_variant		ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.2059-1141G>A		intron_variant		1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106680 AN: 152024 Hom.: 40513 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.702 AC: 106744 AN: 152142 Hom.: 40542 Cov.: 32 AF XY: 0.705 AC XY: 52441 AN XY: 74360

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.743

Alfa AF: 0.814 Hom.: 98703

Bravo AF: 0.689

Asia WGS AF: 0.815 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.3
DANN	Benign	0.65

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: rs1023479; hg19: chr1-172355132;