9-6532607-C-G

Variant names:

• chr9-6532607-C-G
• rs35834773
• NM_000170.3:c.*410G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000170.3(GLDC):​c.*410G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 199,128 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (569 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (24 hom.)
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.368
• Publications: 1 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=-0.41).
• BP6: Variant 9-6532607-C-G is Benign according to our data. Variant chr9-6532607-C-G is described in ClinVar as Benign. ClinVar VariationId is 367165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 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.*410G>C		3_prime_UTR	Exon 25 of 25	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.*410G>C		3_prime_UTR	Exon 25 of 25	ENSP00000370737.4	P23378
	GLDC	ENST00000638233.1	TSL:1	n.1908G>C		non_coding_transcript_exon	Exon 11 of 11
	GLDC	ENST00000920236.1		c.*410G>C		3_prime_UTR	Exon 25 of 25	ENSP00000590295.1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7156 AN: 151946 Hom.: 567 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.00729 AC: 343 AN: 47064 Hom.: 24 Cov.: 0 AF XY: 0.00633 AC XY: 155 AN XY: 24502

African (AFR) AF: 0.168 AC: 274 AN: 1632

American (AMR) AF: 0.00924 AC: 34 AN: 3678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1158

East Asian (EAS) AF: 0.00 AC: 0 AN: 3174

South Asian (SAS) AF: 0.000203 AC: 1 AN: 4918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1766

Middle Eastern (MID) AF: 0.00746 AC: 1 AN: 134

European-Non Finnish (NFE) AF: 0.000496 AC: 14 AN: 28200

Other (OTH) AF: 0.00790 AC: 19 AN: 2404

GnomAD4 genome AF: 0.0471 AC: 7164 AN: 152064 Hom.: 569 Cov.: 32 AF XY: 0.0455 AC XY: 3384 AN XY: 74338

African (AFR) AF: 0.162 AC: 6722 AN: 41428

American (AMR) AF: 0.0197 AC: 301 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 67998

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.00163 Hom.: 2

Bravo AF: 0.0541

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Glycine encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		-0.37
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: rs35834773; hg19: chr9-6532607;