NM_001172774.2:c.337G>T

Variant names:

• chr19-32436454-G-T
• rs1313171017
• NM_001172774.2:c.337G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: DPY19L3 NM_001172774.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.56
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.337G>T	p.Gly113Cys	missense	Exon 5 of 19	NP_001166245.1	Q6ZPD9-1
	DPY19L3	NM_207325.3		c.337G>T	p.Gly113Cys	missense	Exon 5 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.337G>T	p.Gly113Cys	missense	Exon 5 of 19	ENSP00000376081.2	Q6ZPD9-1
	DPY19L3	ENST00000586427.1	TSL:1	c.337G>T	p.Gly113Cys	missense	Exon 5 of 5	ENSP00000466062.1	K7ELG1
	DPY19L3	ENST00000342179.9	TSL:2	c.337G>T	p.Gly113Cys	missense	Exon 5 of 19	ENSP00000344937.4	Q6ZPD9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000459 AC: 1 AN: 217804 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000960

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000443 AC: 6 AN: 1353430 Hom.: 0 Cov.: 26 AF XY: 0.00000594 AC XY: 4 AN XY: 673102

African (AFR) AF: 0.00 AC: 0 AN: 29910

American (AMR) AF: 0.00 AC: 0 AN: 34142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23436

East Asian (EAS) AF: 0.00 AC: 0 AN: 38342

South Asian (SAS) AF: 0.00 AC: 0 AN: 76308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5240

European-Non Finnish (NFE) AF: 0.00000578 AC: 6 AN: 1037870

Other (OTH) AF: 0.00 AC: 0 AN: 56036

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000313 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.9	M
PhyloP100		9.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.63
MVP		0.65
MPC		0.94
ClinPred		0.96	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.42
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs1313171017; hg19: chr19-32927360;