7-34940284-A-C

Variant names:

• chr7-34940284-A-C
• rs771903272
• NM_001366673.1:c.1733T>G

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.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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V578A) has been classified as Uncertain significance.

• 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
• 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, 0.903

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.1733T>G	p.Val578Gly	missense	Exon 19 of 22	NP_001353602.1	A0A1B0GW05
	DPY19L1	NM_015283.2		c.1514T>G	p.Val505Gly	missense	Exon 19 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.1733T>G	p.Val578Gly	missense	Exon 19 of 22	ENSP00000490722.1	A0A1B0GW05
	DPY19L1	ENST00000310974.8	TSL:1	c.1514T>G	p.Val505Gly	missense	Exon 19 of 22	ENSP00000308695.4	Q2PZI1-1
	DPY19L1	ENST00000612226.2	TSL:1	c.695T>G	p.Val232Gly	missense	Exon 10 of 13	ENSP00000478865.2	A0A8J9BZN9

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

⚠️ 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: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4666

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111710

Other (OTH) AF: 0.00 AC: 0 AN: 60234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.6
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
Mutation Taster		=42/58	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: rs771903272; hg19: chr7-34979896;