chr19-32408332-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K27R) has been classified 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172774.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L3	NM_001172774.2	MANE Select	c.79A>G	p.Lys27Glu	missense	Exon 2 of 19	NP_001166245.1	Q6ZPD9-1
	DPY19L3	NM_207325.3		c.79A>G	p.Lys27Glu	missense	Exon 2 of 19	NP_997208.2	Q6ZPD9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L3	ENST00000392250.7	TSL:5 MANE Select	c.79A>G	p.Lys27Glu	missense	Exon 2 of 19	ENSP00000376081.2	Q6ZPD9-1
	DPY19L3	ENST00000586427.1	TSL:1	c.79A>G	p.Lys27Glu	missense	Exon 2 of 5	ENSP00000466062.1	K7ELG1
	DPY19L3	ENST00000587077.6	TSL:1	c.79A>G	p.Lys27Glu	missense	Exon 2 of 3	ENSP00000465995.1	Q8N6Q4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.023
Sift	Benign	0.55	T
Sift4G	Benign	0.16	T
Polyphen		0.35	B
Vest4		0.18
MutPred		0.31		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
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

hg19: chr19-32899238;