rs74461075

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000170.3(GLDC):c.1815C>T(p.Leu605Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,613,850 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

GLDC
NM_000170.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.28

Publications

1 publications found

Variant links:

Genes affected

GLDC (HGNC:4313): (glycine decarboxylase) Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). The protein encoded by this gene is the P protein, which binds to glycine and enables the methylamine group from glycine to be transferred to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH).[provided by RefSeq, Jan 2010]

GLDC Gene-Disease associations (from GenCC):

glycine encephalopathy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen
glycine encephalopathy 1
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
infantile glycine encephalopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
neonatal glycine encephalopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
atypical glycine encephalopathy
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

GLDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 9-6587176-G-A is Benign according to our data. Variant chr9-6587176-G-A is described in ClinVar as Benign. ClinVar VariationId is 367185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1879/152302) while in subpopulation AFR AF = 0.0428 (1777/41550). AF 95% confidence interval is 0.0411. There are 26 homozygotes in GnomAd4. There are 906 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000170.3. 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
	GLDC	NM_000170.3	MANE Select	c.1815C>T	p.Leu605Leu	synonymous	Exon 15 of 25	NP_000161.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GLDC	ENST00000321612.8	TSL:1 MANE Select	c.1815C>T	p.Leu605Leu	synonymous	Exon 15 of 25	ENSP00000370737.4
GLDC	ENST00000639443.1	TSL:1	n.1383C>T		non_coding_transcript_exon	Exon 11 of 21
GLDC	ENST00000639364.1	TSL:5	n.1515C>T		non_coding_transcript_exon	Exon 14 of 24

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1869

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00318

AC:

799

AN:

251474

AF XY:

0.00247

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00132

AC:

1927

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

811

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.0426

AC:

1424

AN:

33460

American (AMR)

AF:

0.00259

AC:

116

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00300

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.000139

AC:

155

AN:

1111832

Other (OTH)

AF:

0.00343

AC:

207

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

194

291

388

485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0123

AC:

1879

AN:

152302

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

906

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0428

AC:

1777

AN:

41550

American (AMR)

AF:

0.00431

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68032

Other (OTH)

AF:

0.0114

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

178

268

357

446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycine encephalopathy (3)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.6

(source)

DANN

Benign

0.77

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over