19-32408332-A-G

Variant names:

• chr19-32408332-A-G
• NM_001172774.2:c.79A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001172774.2(DPY19L3):​c.79A>G​(p.Lys27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DPY19L3 NM_001172774.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.95

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]

ACMG classification

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=0.108704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L3	NM_001172774.2	c.79A>G	p.Lys27Glu	missense_variant	Exon 2 of 19	ENST00000392250.7	NP_001166245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L3	ENST00000392250.7	c.79A>G	p.Lys27Glu	missense_variant	Exon 2 of 19	5	NM_001172774.2	ENSP00000376081.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79A>G (p.K27E) 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 79, causing the lysine (K) at amino acid position 27 to be replaced by a glutamic acid (E). 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	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.078	T;T;T;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.65	T;T;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.97	.;L;.;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	.;N;.;N;.
REVEL	Benign	0.023
Sift	Benign	0.55	.;T;.;T;.
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.35	B;B;.;B;.
Vest4		0.18
MutPred		0.31		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		0.36
MPC		0.38
ClinPred		0.37	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-32899238;