Genetic Variant DPY19L1:p.Lys571Arg (chr7-34940305-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366673.1(DPY19L1):c.1712A>G(p.Lys571Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,608,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

DPY19L1
NM_001366673.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

DPY19L1 (HGNC:22205): (dpy-19 like C-mannosyltransferase 1) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DPY19L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13945246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1 link	c.1712A>G	p.Lys571Arg	missense_variant	Exon 19 of 22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2 link	c.1493A>G	p.Lys498Arg	missense_variant	Exon 19 of 22		NP_056098.1	Q2PZI1-1
DPY19L1	XM_011515246.4 link	c.1625A>G	p.Lys542Arg	missense_variant	Exon 18 of 21		XP_011513548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2 link	c.1712A>G	p.Lys571Arg	missense_variant	Exon 19 of 22	5	NM_001366673.1	ENSP00000490722.1		A0A1B0GW05

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

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:

0.00000816

AC:

AN:

245036

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132888

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1456412

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

724308

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000621

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

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

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

EpiCase

AF:

0.0000547

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

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1493A>G (p.K498R) alteration is located in exon 19 (coding exon 19) of the DPY19L1 gene. This alteration results from a A to G substitution at nucleotide position 1493, causing the lysine (K) at amino acid position 498 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

0.060

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0057

.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

.;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.47

.;N

REVEL

Benign

0.056

Sift

Benign

0.77

.;T

Sift4G

Benign

0.51

.;T

Polyphen

0.031

.;B

Vest4

0.13

MutPred

0.56

.;Loss of methylation at K498 (P = 0.0122);

MVP

0.36

MPC

0.32

ClinPred

0.11

GERP RS

4.1

Varity_R

0.045

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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