7-35013586-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001366673.1(DPY19L1):c.531A>T(p.Arg177Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.205

Genes affected

DPY19L1 (HGNC:22205): (dpy-19 like C-mannosyltransferase 1) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPY19L1	NM_001366673.1	c.531A>T	p.Arg177Ser	missense_variant	4/22	ENST00000638088.2
DPY19L1	NM_015283.2	c.312A>T	p.Arg104Ser	missense_variant	4/22
DPY19L1	XM_011515246.4	c.531A>T	p.Arg177Ser	missense_variant	4/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPY19L1	ENST00000638088.2	c.531A>T	p.Arg177Ser	missense_variant	4/22	5	NM_001366673.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Apr 25, 2022

The c.312A>T (p.R104S) alteration is located in exon 4 (coding exon 4) of the DPY19L1 gene. This alteration results from a A to T substitution at nucleotide position 312, causing the arginine (R) at amino acid position 104 to be replaced by a serine (S). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Benign	0.052
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.75	T
Polyphen		1.0	.;D
Vest4		0.95
MutPred		0.86		.;Gain of ubiquitination at K103 (P = 0.0414);
MVP		0.56
MPC		1.3
ClinPred		1.0	D
GERP RS		-0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-35053198;