7-34940305-T-G

Variant names:

• chr7-34940305-T-G
• rs776936761
• NM_001366673.1:c.1712A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366673.1(DPY19L1):​c.1712A>C​(p.Lys571Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,412 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1712A>C	p.Lys571Thr	missense_variant	Exon 19 of 22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.1493A>C	p.Lys498Thr	missense_variant	Exon 19 of 22		NP_056098.1
DPY19L1	XM_011515246.4	c.1625A>C	p.Lys542Thr	missense_variant	Exon 18 of 21		XP_011513548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1712A>C	p.Lys571Thr	missense_variant	Exon 19 of 22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456412 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724308

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.5	.;D
REVEL	Uncertain	0.31
Sift	Benign	0.12	.;T
Sift4G	Benign	0.096	.;T
Polyphen		0.98	.;D
Vest4		0.65
MutPred		0.59		.;Loss of methylation at K498 (P = 0.0048);
MVP		0.60
MPC		1.1
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs776936761; hg19: chr7-34979917;