19-32437261-C-G

Position:

• chr19-32437261-C-G

Variant summary

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

The NM_001172774.2(DPY19L3):​c.518C>G​(p.Ala173Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.52

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 (HGNC:):

ACMG classification

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	c.518C>G	p.Ala173Gly	missense_variant	6/19	ENST00000392250.7	NP_001166245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L3	ENST00000392250.7	c.518C>G	p.Ala173Gly	missense_variant	6/19	5	NM_001172774.2	ENSP00000376081.2
DPY19L3	ENST00000342179.9	c.518C>G	p.Ala173Gly	missense_variant	6/19	2		ENSP00000344937.4
DPY19L3	ENST00000586987.5	c.518C>G	p.Ala173Gly	missense_variant	6/20	5		ENSP00000466086.1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.518C>G (p.A173G) alteration is located in exon 6 (coding exon 5) of the DPY19L3 gene. This alteration results from a C to G substitution at nucleotide position 518, causing the alanine (A) at amino acid position 173 to be replaced by a glycine (G). 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	0.19
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;.
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M;.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;.;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0060	D;.;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.62	P;.;P
Vest4		0.64
MutPred		0.77		Loss of catalytic residue at A173 (P = 0.0634);Loss of catalytic residue at A173 (P = 0.0634);Loss of catalytic residue at A173 (P = 0.0634);
MVP		0.67
MPC		0.93
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-32928167;