8-94720009-A-G

Position:

• chr8-94720009-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181787.3(DPY19L4):​c.11A>G​(p.Glu4Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPY19L4 NM_181787.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.784

Genes affected

DPY19L4 (HGNC:27829): (dpy-19 like 4) 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16450748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L4	NM_181787.3	c.11A>G	p.Glu4Gly	missense_variant	1/19	ENST00000414645.6	NP_861452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L4	ENST00000414645.6	c.11A>G	p.Glu4Gly	missense_variant	1/19	1	NM_181787.3	ENSP00000389630.2
DPY19L4	ENST00000522422.5	c.11A>G	p.Glu4Gly	missense_variant	1/4	3		ENSP00000428762.1
DPY19L4	ENST00000520774.5	n.11A>G		non_coding_transcript_exon_variant	1/5	5		ENSP00000430162.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Sep 01, 2024

The c.11A>G (p.E4G) alteration is located in exon 1 (coding exon 1) of the DPY19L4 gene. This alteration results from a A to G substitution at nucleotide position 11, causing the glutamic acid (E) at amino acid position 4 to be replaced by a glycine (G). 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	Benign	0.072
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	.;T
Eigen	Benign	0.039
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.95	.;P
Vest4		0.25
MutPred		0.12		Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);
MVP		0.58
MPC		0.57
ClinPred		0.75	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.15
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs1810381215; hg19: chr8-95732237; COSMIC: COSV68963572;