rs10975641

Variant names:

• chr9-6556839-C-G
• rs10975641
• NM_000170.3:c.2053-537G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-6556839-C-G
• chr9-6556839-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000170.3(GLDC):​c.2053-537G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,602 control chromosomes in the GnomAD database, including 10,206 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 0.36 (10206 hom., cov: 31)
• Consequence: GLDC NM_000170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDC	NM_000170.3	c.2053-537G>C		intron_variant	Intron 17 of 24	ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612.8	c.2053-537G>C		intron_variant	Intron 17 of 24	1	NM_000170.3	ENSP00000370737.4

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55167 AN: 151488 Hom.: 10197 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.364 AC: 55198 AN: 151602 Hom.: 10206 Cov.: 31 AF XY: 0.364 AC XY: 26955 AN XY: 74042

African (AFR) AF: 0.384 AC: 15854 AN: 41294

American (AMR) AF: 0.364 AC: 5551 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2181 AN: 5156

South Asian (SAS) AF: 0.372 AC: 1785 AN: 4804

European-Finnish (FIN) AF: 0.352 AC: 3675 AN: 10430

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23937 AN: 67892

Other (OTH) AF: 0.363 AC: 763 AN: 2102

Alfa AF: 0.334 Hom.: 1053

Bravo AF: 0.367

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.39
PhyloP100		-1.7
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: rs10975641; hg19: chr9-6556839;