rs2012353

Positions:

• chr19-32408387-G-A

Variant summary

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

The NM_001172774.2(DPY19L3):​c.103+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,543,030 control chromosomes in the GnomAD database, including 22,499 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 0.17 (2242 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20257 hom.)
• Consequence: DPY19L3 NM_001172774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

DPY19L3 (HGNC:27120): (dpy-19 like C-mannosyltransferase 3) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan. Predicted to be integral component of membrane. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPY19L3	NM_001172774.2	c.103+31G>A		intron_variant		ENST00000392250.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPY19L3	ENST00000392250.7	c.103+31G>A		intron_variant		5	NM_001172774.2	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25928 AN: 151978 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.173 AC: 41245 AN: 238424 Hom.: 3568 AF XY: 0.172 AC XY: 22168 AN XY: 128964

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.169 AC: 235094 AN: 1390934 Hom.: 20257 Cov.: 22 AF XY: 0.168 AC XY: 116998 AN XY: 695688

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.171 AC: 25950 AN: 152096 Hom.: 2242 Cov.: 32 AF XY: 0.171 AC XY: 12742 AN XY: 74376

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.165

Alfa AF: 0.165 Hom.: 2167

Bravo AF: 0.168

Asia WGS AF: 0.125 AC: 437 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	9.5
DANN	Benign	0.55

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: rs2012353; hg19: chr19-32899293; COSMIC: COSV60477366; COSMIC: COSV60477366;