Variant 19-32408263-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172774.2(DPY19L3):c.10A>C(p.Ile4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

DPY19L3
NM_001172774.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.822

Variant links:

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]

DPY19L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06385562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L3	NM_001172774.2 link	c.10A>C	p.Ile4Leu	missense_variant	2/19	ENST00000392250.7	NP_001166245.1	Q6ZPD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L3	ENST00000392250.7 link	c.10A>C	p.Ile4Leu	missense_variant	2/19	5	NM_001172774.2	ENSP00000376081.2		Q6ZPD9-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250912

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1460322

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.10A>C (p.I4L) alteration is located in exon 2 (coding exon 1) of the DPY19L3 gene. This alteration results from a A to C substitution at nucleotide position 10, causing the isoleucine (I) at amino acid position 4 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.022

T;T;T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.57

T;T;T;.;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.064

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.;L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.14

.;N;.;N;.

REVEL

Benign

0.040

Sift

Benign

0.82

.;T;.;T;.

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.10

B;B;.;B;.

Vest4

0.40

MVP

0.25

MPC

0.27

ClinPred

0.023

GERP RS

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over