chr19-32439893-A-T

Variant names:

• chr19-32439893-A-T
• rs746399509
• NM_001172774.2:c.838A>T

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.838A>T​(p.Met280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M280V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPY19L3 NM_001172774.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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=0.07591793).

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.838A>T	p.Met280Leu	missense	Exon 8 of 19	NP_001166245.1	Q6ZPD9-1
	DPY19L3	NM_207325.3		c.838A>T	p.Met280Leu	missense	Exon 8 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.838A>T	p.Met280Leu	missense	Exon 8 of 19	ENSP00000376081.2	Q6ZPD9-1
	DPY19L3	ENST00000342179.9	TSL:2	c.838A>T	p.Met280Leu	missense	Exon 8 of 19	ENSP00000344937.4	Q6ZPD9-1
	DPY19L3	ENST00000852724.1		c.838A>T	p.Met280Leu	missense	Exon 8 of 19	ENSP00000522783.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461032 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726798

⚠️ 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: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111658

Other (OTH) AF: 0.00 AC: 0 AN: 60366

⚠️ 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.: 33

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.71
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.055	N
PhyloP100		2.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.077
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.57		Gain of ubiquitination at K285 (P = 0.0693)
MVP		0.21
MPC		0.26
ClinPred		0.80	D
GERP RS		5.8
Varity_R		0.11
gMVP		0.20
Mutation Taster		=85/15	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

dbSNP: rs746399509; hg19: chr19-32930799;