NM_000170.3:c.*473C>T

Variant names:

• chr9-6532544-G-A
• rs1061407
• NM_000170.3:c.*473C>T

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.*473C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 156,572 control chromosomes in the GnomAD database, including 36,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35599 hom., cov: 29)
  • Exomes 𝑓: 0.62 (1057 hom.)
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.397
• Publications: 7 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=-0.91).
• BP6: Variant 9-6532544-G-A is Benign according to our data. Variant chr9-6532544-G-A is described in ClinVar as Benign. ClinVar VariationId is 367164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 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.*473C>T		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.*473C>T		3_prime_UTR	Exon 25 of 25	ENSP00000370737.4	P23378
	GLDC	ENST00000638233.1	TSL:1	n.1971C>T		non_coding_transcript_exon	Exon 11 of 11
	GLDC	ENST00000920236.1		c.*473C>T		3_prime_UTR	Exon 25 of 25	ENSP00000590295.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103052 AN: 151218 Hom.: 35575 Cov.: 29

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.623 AC: 3265 AN: 5244 Hom.: 1057 Cov.: 0 AF XY: 0.624 AC XY: 1723 AN XY: 2760

African (AFR) AF: 0.643 AC: 9 AN: 14

American (AMR) AF: 0.708 AC: 786 AN: 1110

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 11 AN: 24

East Asian (EAS) AF: 0.917 AC: 77 AN: 84

South Asian (SAS) AF: 0.603 AC: 334 AN: 554

European-Finnish (FIN) AF: 0.707 AC: 324 AN: 458

Middle Eastern (MID) AF: 0.500 AC: 3 AN: 6

European-Non Finnish (NFE) AF: 0.570 AC: 1598 AN: 2802

Other (OTH) AF: 0.641 AC: 123 AN: 192

GnomAD4 genome AF: 0.682 AC: 103131 AN: 151328 Hom.: 35599 Cov.: 29 AF XY: 0.688 AC XY: 50846 AN XY: 73894

African (AFR) AF: 0.704 AC: 29035 AN: 41216

American (AMR) AF: 0.722 AC: 10983 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2174 AN: 3468

East Asian (EAS) AF: 0.949 AC: 4892 AN: 5156

South Asian (SAS) AF: 0.706 AC: 3396 AN: 4808

European-Finnish (FIN) AF: 0.736 AC: 7589 AN: 10310

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43167 AN: 67858

Other (OTH) AF: 0.641 AC: 1342 AN: 2094

Alfa AF: 0.651 Hom.: 10811

Bravo AF: 0.681

Asia WGS AF: 0.809 AC: 2809 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		-0.40
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: rs1061407; hg19: chr9-6532544;