rs2282160

Variant names:

• chr9-6534845-T-C
• rs2282160
• NM_000170.3:c.2839-57A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-6534845-T-C
• chr9-6534845-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000170.3(GLDC):​c.2839-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 900,590 control chromosomes in the GnomAD database, including 92,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14111 hom., cov: 32)
  • Exomes 𝑓: 0.45 (78755 hom.)
• Consequence: GLDC NM_000170.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.15
• Publications: 14 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-6534845-T-C is Benign according to our data. Variant chr9-6534845-T-C is described in ClinVar as Benign. ClinVar VariationId is 1185161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDC	NM_000170.3	MANE Select	c.2839-57A>G		intron	N/A	NP_000161.2	P23378

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDC	ENST00000321612.8	TSL:1 MANE Select	c.2839-57A>G		intron	N/A	ENSP00000370737.4	P23378
	GLDC	ENST00000638233.1	TSL:1	n.1274-57A>G		intron	N/A
	GLDC	ENST00000639443.1	TSL:1	n.2407-57A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64562 AN: 151866 Hom.: 14112 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.455 AC: 340517 AN: 748606 Hom.: 78755 AF XY: 0.454 AC XY: 180623 AN XY: 397966

African (AFR) AF: 0.356 AC: 7126 AN: 20014

American (AMR) AF: 0.595 AC: 24042 AN: 40412

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 7125 AN: 21304

East Asian (EAS) AF: 0.505 AC: 18232 AN: 36068

South Asian (SAS) AF: 0.457 AC: 31714 AN: 69444

European-Finnish (FIN) AF: 0.449 AC: 23118 AN: 51522

Middle Eastern (MID) AF: 0.455 AC: 2012 AN: 4418

European-Non Finnish (NFE) AF: 0.451 AC: 211135 AN: 468600

Other (OTH) AF: 0.435 AC: 16013 AN: 36824

GnomAD4 genome AF: 0.425 AC: 64587 AN: 151984 Hom.: 14111 Cov.: 32 AF XY: 0.428 AC XY: 31769 AN XY: 74268

African (AFR) AF: 0.349 AC: 14464 AN: 41440

American (AMR) AF: 0.511 AC: 7803 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2531 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2171 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4538 AN: 10566

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30631 AN: 67946

Other (OTH) AF: 0.405 AC: 854 AN: 2110

Alfa AF: 0.433 Hom.: 21031

Bravo AF: 0.427

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycine encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.46
PhyloP100		-3.2
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2282160; hg19: chr9-6534845; COSMIC: COSV58680407; COSMIC: COSV58680407;