7-34941828-C-T

Variant names:

• chr7-34941828-C-T
• NM_001366673.1:c.1626G>A

Variant summary

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

The NM_001366673.1(DPY19L1):​c.1626G>A​(p.Met542Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79

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, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1626G>A	p.Met542Ile	missense_variant	Exon 18 of 22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.1407G>A	p.Met469Ile	missense_variant	Exon 18 of 22		NP_056098.1
DPY19L1	XM_011515246.4	c.1539G>A	p.Met513Ile	missense_variant	Exon 17 of 21		XP_011513548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1626G>A	p.Met542Ile	missense_variant	Exon 18 of 22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1407G>A (p.M469I) alteration is located in exon 18 (coding exon 18) of the DPY19L1 gene. This alteration results from a G to A substitution at nucleotide position 1407, causing the methionine (M) at amino acid position 469 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0050	.;D
Sift4G	Uncertain	0.013	.;D
Polyphen		0.97	.;D
Vest4		0.83
MutPred		0.77		.;Gain of methylation at K472 (P = 0.1085);
MVP		0.66
MPC		1.2
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.63
gMVP		0.83

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: chr7-34981440;