18-49038189-T-C

Position:

• chr18-49038189-T-C

Variant summary

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

The NM_001353214.3(DYM):​c.*5866A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,066 control chromosomes in the GnomAD database, including 33,483 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 (33483 hom., cov: 31)
• Consequence: DYM NM_001353214.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602

Genes affected

DYM (HGNC:21317): (dymeclin) This gene encodes a protein which regulates Golgi-associated secretory pathways that are essential to endochondral bone formation during early development. This gene is also believed to play a role in early brain development. This gene is widely expressed in embryos and is particularly abundant in chodrocytes and brain tissues. It encodes a peripheral membrane protein which shuttles between the cytosol and Golgi complex. Mutations in this gene are associated with two types of recessive osteochondrodysplasia: Dyggve-Melchior-Clausen (DMC) dysplasia and Smith-McCort (SMC) dysplasia. [provided by RefSeq, Jun 2017]

DYM-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYM	NM_001353214.3	c.*5866A>G		3_prime_UTR_variant	18/18	ENST00000675505.1	NP_001340143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505	c.*5866A>G		3_prime_UTR_variant	18/18		NM_001353214.3	ENSP00000501694.1
DYM-AS1	ENST00000584252.1	n.243-1811T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95423 AN: 151948 Hom.: 33476 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.628 AC: 95449 AN: 152066 Hom.: 33483 Cov.: 31 AF XY: 0.623 AC XY: 46289 AN XY: 74326

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.708

Alfa AF: 0.765 Hom.: 92325

Bravo AF: 0.622

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs833520; hg19: chr18-46564559;