chr14-91170188-C-G

Variant names:

• chr14-91170188-C-G
• rs4900072
• NM_001102368.3:c.443C>G

Variant summary

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

The NM_024952.8(DGLUCY):​c.441+2C>G variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DGLUCY NM_024952.8 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 28 publications found

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

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 (REVEL=0.029).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024952.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGLUCY	NM_001102368.3	MANE Select	c.443C>G	p.Ala148Gly	missense	Exon 5 of 14	NP_001095838.1
	DGLUCY	NM_001286470.2		c.443C>G	p.Ala148Gly	missense	Exon 8 of 17	NP_001273399.1
	DGLUCY	NM_001358310.2		c.443C>G	p.Ala148Gly	missense	Exon 5 of 14	NP_001345239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGLUCY	ENST00000256324.15	TSL:1 MANE Select	c.443C>G	p.Ala148Gly	missense	Exon 5 of 14	ENSP00000256324.9
	DGLUCY	ENST00000521077.6	TSL:1	c.443C>G	p.Ala148Gly	missense	Exon 7 of 15	ENSP00000430137.1
	DGLUCY	ENST00000517518.5	TSL:1	c.443C>G	p.Ala148Gly	missense	Exon 6 of 11	ENSP00000428652.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 13707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.75
DANN	Benign	0.41
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.048	N
M_CAP	Benign	0.0089	T
PhyloP100		-0.54
ClinPred		0.31	T
GERP RS		-5.0
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -13

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

Other links and lift over

dbSNP: rs4900072; hg19: chr14-91636532;