7-34938106-T-C

Variant names:

• chr7-34938106-T-C
• rs1177737159
• NM_001366673.1:c.1978A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366673.1(DPY19L1):​c.1978A>G​(p.Ile660Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.960
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16062796).

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.1978A>G	p.Ile660Val	missense	Exon 21 of 22	NP_001353602.1	A0A1B0GW05
	DPY19L1	NM_015283.2		c.1759A>G	p.Ile587Val	missense	Exon 21 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.1978A>G	p.Ile660Val	missense	Exon 21 of 22	ENSP00000490722.1	A0A1B0GW05
	DPY19L1	ENST00000310974.8	TSL:1	c.1759A>G	p.Ile587Val	missense	Exon 21 of 22	ENSP00000308695.4	Q2PZI1-1
	DPY19L1	ENST00000612226.2	TSL:1	c.940A>G	p.Ile314Val	missense	Exon 12 of 13	ENSP00000478865.2	A0A8J9BZN9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460606 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726590

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.0000225 AC: 1 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111714

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68054

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	Benign	0.065
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.70
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.96
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.087
Sift	Benign	0.78	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.56		Gain of catalytic residue at I587 (P = 0.0486)
MVP		0.29
MPC		0.32
ClinPred		0.19	T
GERP RS		4.5
Varity_R		0.037
gMVP		0.43
Mutation Taster		=93/7	polymorphism

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: rs1177737159; hg19: chr7-34977718;