rs111326356

Variant names:

• chr9-6532760-C-T
• rs111326356
• NM_000170.3:c.*257G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-6532760-C-T
• chr9-6532760-C-A
• chr9-6532760-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000170.3(GLDC):​c.*257G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 473,368 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (9 hom.)
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.697
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-6532760-C-T is Benign according to our data. Variant chr9-6532760-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 367166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00975 (1485/152258) while in subpopulation AFR AF = 0.033 (1369/41534). AF 95% confidence interval is 0.0315. There are 28 homozygotes in GnomAd4. There are 708 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLDC	NM_000170.3	MANE Select	c.*257G>A		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.*257G>A		3_prime_UTR	Exon 25 of 25	ENSP00000370737.4	P23378
	GLDC	ENST00000638233.1	TSL:1	n.1755G>A		non_coding_transcript_exon	Exon 11 of 11
	GLDC	ENST00000920236.1		c.*257G>A		3_prime_UTR	Exon 25 of 25	ENSP00000590295.1

Frequencies

GnomAD3 genomes AF: 0.00972 AC: 1479 AN: 152140 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00168 AC: 538 AN: 321110 Hom.: 9 Cov.: 0 AF XY: 0.00140 AC XY: 238 AN XY: 170608

African (AFR) AF: 0.0323 AC: 309 AN: 9552

American (AMR) AF: 0.00225 AC: 33 AN: 14696

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 22 AN: 9730

East Asian (EAS) AF: 0.000203 AC: 4 AN: 19702

South Asian (SAS) AF: 0.0000994 AC: 4 AN: 40228

European-Finnish (FIN) AF: 0.0000578 AC: 1 AN: 17314

Middle Eastern (MID) AF: 0.00761 AC: 10 AN: 1314

European-Non Finnish (NFE) AF: 0.000583 AC: 111 AN: 190514

Other (OTH) AF: 0.00244 AC: 44 AN: 18060

GnomAD4 genome AF: 0.00975 AC: 1485 AN: 152258 Hom.: 28 Cov.: 32 AF XY: 0.00951 AC XY: 708 AN XY: 74432

African (AFR) AF: 0.0330 AC: 1369 AN: 41534

American (AMR) AF: 0.00353 AC: 54 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.0109

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.81
CADD	Benign	7.4
DANN	Benign	0.74
PhyloP100		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs111326356; hg19: chr9-6532760;