chr19-32436454-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001172774.2(DPY19L3):​c.337G>A​(p.Gly113Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,432 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G113C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: DPY19L3 NM_001172774.2 missense
• Clinical Significance: Not reported in ClinVar
• 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>A	p.Gly113Ser	missense	Exon 5 of 19	NP_001166245.1	Q6ZPD9-1
	DPY19L3	NM_207325.3		c.337G>A	p.Gly113Ser	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>A	p.Gly113Ser	missense	Exon 5 of 19	ENSP00000376081.2	Q6ZPD9-1
	DPY19L3	ENST00000586427.1	TSL:1	c.337G>A	p.Gly113Ser	missense	Exon 5 of 5	ENSP00000466062.1	K7ELG1
	DPY19L3	ENST00000342179.9	TSL:2	c.337G>A	p.Gly113Ser	missense	Exon 5 of 19	ENSP00000344937.4	Q6ZPD9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353432 Hom.: 0 Cov.: 26 AF XY: 0.00000149 AC XY: 1 AN XY: 673104

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 76310

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: 0.00 AC: 0 AN: 1037870

Other (OTH) AF: 0.0000178 AC: 1 AN: 56036

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.19
Sift	Benign	0.11	T
Sift4G	Benign	0.35	T
Polyphen		0.92	P
Vest4		0.49
MutPred		0.45		Gain of disorder (P = 0.0749)
MVP		0.68
MPC		0.34
ClinPred		0.93	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.32
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;