chr1-172084147-T-C

Variant names:

• chr1-172084147-T-C
• rs17346452
• NM_015569.5:c.1493+2245T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015569.5(DNM3):​c.1493+2245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,080 control chromosomes in the GnomAD database, including 3,510 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 0.18 (3510 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1493+2245T>C		intron_variant	Intron 12 of 20	ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1493+2245T>C		intron_variant	Intron 12 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28131 AN: 151962 Hom.: 3509 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.185 AC: 28129 AN: 152080 Hom.: 3510 Cov.: 32 AF XY: 0.181 AC XY: 13434 AN XY: 74348

African (AFR) AF: 0.0460 AC: 1911 AN: 41550

American (AMR) AF: 0.161 AC: 2458 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3468

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5180

South Asian (SAS) AF: 0.203 AC: 976 AN: 4818

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18986 AN: 67932

Other (OTH) AF: 0.208 AC: 438 AN: 2106

Alfa AF: 0.229 Hom.: 5994

Bravo AF: 0.173

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17346452; hg19: chr1-172053287;