rs771903272

Variant names:

• chr7-34940284-A-C
• NM_001366673.1:c.1733T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-34940284-A-C
• chr7-34940284-A-G

Variant summary

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

The NM_001366673.1(DPY19L1):​c.1733T>G​(p.Val578Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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]

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, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1733T>G	p.Val578Gly	missense_variant	Exon 19 of 22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.1514T>G	p.Val505Gly	missense_variant	Exon 19 of 22		NP_056098.1
DPY19L1	XM_011515246.4	c.1646T>G	p.Val549Gly	missense_variant	Exon 18 of 21		XP_011513548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1733T>G	p.Val578Gly	missense_variant	Exon 19 of 22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459246 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725868

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.9	.;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0020	.;D
Polyphen		1.0	.;D
Vest4		0.66
MutPred		0.73		.;Loss of stability (P = 0.0494);
MVP		0.58
MPC		1.2
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.87
gMVP		0.88

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: chr7-34979896;