7-34939282-C-A

Variant names:

• chr7-34939282-C-A
• rs1042610257
• NM_001366673.1:c.1958G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001366673.1(DPY19L1):​c.1958G>T​(p.Gly653Val) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G653A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 0 publications found

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]

ENSG00000294671 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366673.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L1	NM_001366673.1	MANE Select	c.1958G>T	p.Gly653Val	missense	Exon 20 of 22	NP_001353602.1	A0A1B0GW05
	DPY19L1	NM_015283.2		c.1739G>T	p.Gly580Val	missense	Exon 20 of 22	NP_056098.1	Q2PZI1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L1	ENST00000638088.2	TSL:5 MANE Select	c.1958G>T	p.Gly653Val	missense	Exon 20 of 22	ENSP00000490722.1	A0A1B0GW05
	DPY19L1	ENST00000310974.8	TSL:1	c.1739G>T	p.Gly580Val	missense	Exon 20 of 22	ENSP00000308695.4	Q2PZI1-1
	DPY19L1	ENST00000612226.2	TSL:1	c.920G>T	p.Gly307Val	missense	Exon 11 of 13	ENSP00000478865.2	A0A8J9BZN9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.67		Loss of disorder (P = 0.0697)
MVP		0.52
MPC		1.1
ClinPred		0.97	D
GERP RS		5.9
PromoterAI		0.0086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.88
Mutation Taster		=35/65	disease causing

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

Other links and lift over

dbSNP: rs1042610257; hg19: chr7-34978894;