rs564887735

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-34947670-A-C
• chr7-34947670-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001366673.1(DPY19L1):​c.1454T>G​(p.Leu485Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,450 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1454T>G	p.Leu485Arg	missense_variant	Exon 15 of 22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.1235T>G	p.Leu412Arg	missense_variant	Exon 15 of 22		NP_056098.1
DPY19L1	XM_011515246.4	c.1367T>G	p.Leu456Arg	missense_variant	Exon 14 of 21		XP_011513548.1
LOC102724723	XR_001745166.2	n.173-759A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1454T>G	p.Leu485Arg	missense_variant	Exon 15 of 22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460450 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726562

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Uncertain	0.0038	D
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.1	.;D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.024	.;D;D
Sift4G	Pathogenic	0.0010	.;D;.
Polyphen		1.0	.;D;.
Vest4		0.96
MutPred		0.86		.;Gain of MoRF binding (P = 0.0118);.;
MVP		0.62
MPC		1.4
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-34987282;