7-34947670-A-G

Variant names:

• chr7-34947670-A-G
• rs564887735
• NM_001366673.1:c.1454T>C

Variant summary

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

The NM_001366673.1(DPY19L1):​c.1454T>C​(p.Leu485Pro) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65

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]

LOC102724723 (HGNC:):

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, 0.922

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1454T>C	p.Leu485Pro	missense_variant	Exon 15 of 22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.1235T>C	p.Leu412Pro	missense_variant	Exon 15 of 22		NP_056098.1
DPY19L1	XM_011515246.4	c.1367T>C	p.Leu456Pro	missense_variant	Exon 14 of 21		XP_011513548.1
LOC102724723	XR_001745166.2	n.173-759A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1454T>C	p.Leu485Pro	missense_variant	Exon 15 of 22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1235T>C (p.L412P) alteration is located in exon 15 (coding exon 15) of the DPY19L1 gene. This alteration results from a T to C substitution at nucleotide position 1235, causing the leucine (L) at amino acid position 412 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	0.94
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	.;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	-0.086	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.7	.;D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	.;D;.
Polyphen		1.0	.;D;.
Vest4		0.93
MutPred		0.80		.;Loss of stability (P = 0.0324);.;
MVP		0.59
MPC		1.5
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.94
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs564887735; hg19: chr7-34987282;