rs7146008

Positions:

• chr14-91126957-A-G
• chr14-91126957-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102368.3(DGLUCY):​c.-82+12674A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,416 control chromosomes in the GnomAD database, including 28,113 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28113 hom., cov: 29)
• Consequence: DGLUCY NM_001102368.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

Genes affected

DGLUCY (HGNC:20498): (D-glutamate cyclase) Predicted to enable D-glutamate cyclase activity. Predicted to be involved in glutamate metabolic process. Predicted to be located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGLUCY	NM_001102368.3	c.-82+12674A>G		intron_variant		ENST00000256324.15	NP_001095838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGLUCY	ENST00000256324.15	c.-82+12674A>G		intron_variant		1	NM_001102368.3	ENSP00000256324	P3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90103 AN: 151308 Hom.: 28098 Cov.: 29

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.595 AC: 90157 AN: 151416 Hom.: 28113 Cov.: 29 AF XY: 0.603 AC XY: 44583 AN XY: 73894

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.630

Alfa AF: 0.645 Hom.: 64010

Bravo AF: 0.586

Asia WGS AF: 0.797 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.13
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs7146008; hg19: chr14-91593301;