7-34958006-G-A

Position:

• chr7-34958006-G-A

Variant summary

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

The NM_001366673.1(DPY19L1):​c.1157C>T​(p.Ala386Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

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]

DPY19L1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1157C>T	p.Ala386Val	missense_variant	11/22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.938C>T	p.Ala313Val	missense_variant	11/22		NP_056098.1
DPY19L1	XM_011515246.4	c.1093-2639C>T		intron_variant			XP_011513548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1157C>T	p.Ala386Val	missense_variant	11/22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1428926 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 711014

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

May 05, 2023

The c.938C>T (p.A313V) alteration is located in exon 11 (coding exon 11) of the DPY19L1 gene. This alteration results from a C to T substitution at nucleotide position 938, causing the alanine (A) at amino acid position 313 to be replaced by a valine (V). 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	0.27
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	.;N
REVEL	Benign	0.26
Sift	Benign	0.22	.;T
Sift4G	Benign	0.25	.;T
Polyphen		1.0	.;D
Vest4		0.87
MutPred		0.75		.;Gain of glycosylation at T309 (P = 0.3032);
MVP		0.70
MPC		0.83
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.28		Position offset: -22

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: chr7-34997618;