Variant 19-32432805-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001172774.2(DPY19L3):c.327A>T(p.Gln109His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000205 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DPY19L3
NM_001172774.2 missense, splice_region

Scores

Splicing: ADA: 0.9472

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4119911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L3	NM_001172774.2 linkuse as main transcript	c.327A>T	p.Gln109His	missense_variant, splice_region_variant	4/19	ENST00000392250.7	NP_001166245.1	Q6ZPD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DPY19L3	ENST00000392250.7 linkuse as main transcript	c.327A>T	p.Gln109His	missense_variant, splice_region_variant	4/19	5	NM_001172774.2	ENSP00000376081.2	Q6ZPD9-1
DPY19L3	ENST00000586427.1 linkuse as main transcript	c.327A>T	p.Gln109His	missense_variant, splice_region_variant	4/5	1		ENSP00000466062.1	K7ELG1
DPY19L3	ENST00000342179.9 linkuse as main transcript	c.327A>T	p.Gln109His	missense_variant, splice_region_variant	4/19	2		ENSP00000344937.4	Q6ZPD9-1
DPY19L3	ENST00000586987.5 linkuse as main transcript	c.327A>T	p.Gln109His	missense_variant, splice_region_variant	4/20	5		ENSP00000466086.1	K7ELH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251204

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135772

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726958

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Aug 26, 2024

The c.327A>T (p.Q109H) alteration is located in exon 4 (coding exon 3) of the DPY19L3 gene. This alteration results from a A to T substitution at nucleotide position 327, causing the glutamine (Q) at amino acid position 109 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.022

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.66

T;T;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.94

L;.;L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;.;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.018

D;.;D;.

Sift4G

Uncertain

0.029

D;D;D;D

Polyphen

0.0070

B;.;B;.

Vest4

0.23

MutPred

0.57

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.48

MPC

0.29

ClinPred

0.83

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.12

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.70

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.36

Position offset: 1

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