rs4072117

Variant names:

• chr1-172239731-T-C
• rs4072117
• NM_015569.5:c.1660-13842T>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.1660-13842T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,514 control chromosomes in the GnomAD database, including 2,426 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 0.16 (2426 hom., cov: 30)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1660-13842T>C		intron_variant	Intron 14 of 20	ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1660-13842T>C		intron_variant	Intron 14 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24935 AN: 151404 Hom.: 2422 Cov.: 30

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.165 AC: 24958 AN: 151514 Hom.: 2426 Cov.: 30 AF XY: 0.163 AC XY: 12043 AN XY: 73958

African (AFR) AF: 0.0568 AC: 2353 AN: 41420

American (AMR) AF: 0.191 AC: 2896 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1235 AN: 5104

South Asian (SAS) AF: 0.190 AC: 912 AN: 4796

European-Finnish (FIN) AF: 0.179 AC: 1865 AN: 10416

Middle Eastern (MID) AF: 0.161 AC: 46 AN: 286

European-Non Finnish (NFE) AF: 0.213 AC: 14458 AN: 67826

Other (OTH) AF: 0.176 AC: 370 AN: 2104

Alfa AF: 0.169 Hom.: 496

Bravo AF: 0.164

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.69
PhyloP100		-0.95
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: rs4072117; hg19: chr1-172208871;