chr7-34955310-A-G

Variant names:

• chr7-34955310-A-G
• rs1784355006
• NM_001366673.1:c.1237T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001366673.1(DPY19L1):​c.1237T>C​(p.Trp413Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000375 in 1,600,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DPY19L1 NM_001366673.1 missense, splice_region
• Scores: Splicing: ADA: 0.5767
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

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.1237T>C	p.Trp413Arg	missense splice_region	Exon 12 of 22	NP_001353602.1	A0A1B0GW05
	DPY19L1	NM_015283.2		c.1018T>C	p.Trp340Arg	missense splice_region	Exon 12 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.1237T>C	p.Trp413Arg	missense splice_region	Exon 12 of 22	ENSP00000490722.1	A0A1B0GW05
	DPY19L1	ENST00000310974.8	TSL:1	c.1018T>C	p.Trp340Arg	missense splice_region	Exon 12 of 22	ENSP00000308695.4	Q2PZI1-1
	DPY19L1	ENST00000612226.2	TSL:1	c.199T>C	p.Trp67Arg	missense splice_region	Exon 3 of 13	ENSP00000478865.2	A0A8J9BZN9

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151934 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1448238 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 721200

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32808

American (AMR) AF: 0.0000460 AC: 2 AN: 43470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39444

South Asian (SAS) AF: 0.00 AC: 0 AN: 85274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102560

Other (OTH) AF: 0.0000167 AC: 1 AN: 59806

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000173310), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151934 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74198

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67866

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.086	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.80		Loss of helix (P = 0.0376)
MVP		0.64
MPC		1.5
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.77
gMVP		0.81
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.58
dbscSNV1_RF	Benign	0.46
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: rs1784355006; hg19: chr7-34994922;