Variant chr19-32408333-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001172774.2(DPY19L3):c.80A>G(p.Lys27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DPY19L3
NM_001172774.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

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:

DPY19L3 (HGNC:):

DPY19L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L3	NM_001172774.2 linkuse as main transcript	c.80A>G	p.Lys27Arg	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 linkuse as main transcript	c.80A>G	p.Lys27Arg	missense_variant	2/19	5	NM_001172774.2	ENSP00000376081.2		Q6ZPD9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 20, 2024

The c.80A>G (p.K27R) alteration is located in exon 2 (coding exon 1) of the DPY19L3 gene. This alteration results from a A to G substitution at nucleotide position 80, causing the lysine (K) at amino acid position 27 to be replaced by an arginine (R). 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

0.074

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

T;T;T;T;T

Eigen

Benign

-0.083

Eigen_PC

Benign

-0.0020

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

T;T;T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.97

.;L;.;L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

.;N;.;N;.

REVEL

Benign

0.096

Sift

Benign

0.29

.;T;.;T;.

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.99

D;P;.;P;.

Vest4

0.32

MutPred

0.29

Loss of ubiquitination at K27 (P = 0.002);Loss of ubiquitination at K27 (P = 0.002);Loss of ubiquitination at K27 (P = 0.002);Loss of ubiquitination at K27 (P = 0.002);Loss of ubiquitination at K27 (P = 0.002);

MVP

0.26

MPC

0.25

ClinPred

0.31

GERP RS

3.5

Varity_R

0.052

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: 0

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