Genetic Variant DPY19L3:p.Gly113Cys (chr19-32436454-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001172774.2(DPY19L3):c.337G>T(p.Gly113Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000443 in 1,353,430 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

DPY19L3
NM_001172774.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56

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:

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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 rank	MANE	Protein	UniProt
DPY19L3	NM_001172774.2 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 5 of 19	ENST00000392250.7	NP_001166245.1	Q6ZPD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DPY19L3	ENST00000392250.7 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 5 of 19	5	NM_001172774.2	ENSP00000376081.2	Q6ZPD9-1
DPY19L3	ENST00000586427.1 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 5 of 5	1		ENSP00000466062.1	K7ELG1
DPY19L3	ENST00000342179.9 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 5 of 19	2		ENSP00000344937.4	Q6ZPD9-1
DPY19L3	ENST00000586987.5 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 5 of 20	5		ENSP00000466086.1	K7ELH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000459

AC:

AN:

217804

Hom.:

AF XY:

0.00

AC XY:

AN XY:

118318

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:

0.00000960

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000443

AC:

AN:

1353430

Hom.:

Cov.:

AF XY:

0.00000594

AC XY:

AN XY:

673102

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:

0.00000578

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337G>T (p.G113C) alteration is located in exon 5 (coding exon 4) of the DPY19L3 gene. This alteration results from a G to T substitution at nucleotide position 337, causing the glycine (G) at amino acid position 113 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;D;.;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.9

M;.;M;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.6

N;.;N;.

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;.;D;.

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.63

MVP

0.65

MPC

0.94

ClinPred

0.96

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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