8-94739765-A-C

Position:

• chr8-94739765-A-C

Variant summary

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

The NM_181787.3(DPY19L4):​c.586A>C​(p.Thr196Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DPY19L4 NM_181787.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L4	NM_181787.3	c.586A>C	p.Thr196Pro	missense_variant	6/19	ENST00000414645.6	NP_861452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L4	ENST00000414645.6	c.586A>C	p.Thr196Pro	missense_variant	6/19	1	NM_181787.3	ENSP00000389630.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 14, 2024

The c.586A>C (p.T196P) alteration is located in exon 6 (coding exon 6) of the DPY19L4 gene. This alteration results from a A to C substitution at nucleotide position 586, causing the threonine (T) at amino acid position 196 to be replaced by a proline (P). 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	0.78
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;T;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D;T;T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.82
MutPred		0.82		.;Loss of MoRF binding (P = 0.1462);.;.;
MVP		0.53
MPC		0.60
ClinPred		0.94	D
GERP RS		6.0
Varity_R		0.76
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-95751993;