rs7848919

Variant names:

• chr9-6532477-G-A
• rs7848919
• NM_000170.3:c.*540C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-6532477-G-A
• chr9-6532477-G-C
• chr9-6532477-G-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.*540C>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 0.707 in 154,584 control chromosomes in the GnomAD database, including 38,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38283 hom., cov: 29)
  • Exomes 𝑓: 0.63 (673 hom.)
• Consequence: GLDC NM_000170.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.693
• 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=-0.9).
• BP6: Variant 9-6532477-G-A is Benign according to our data. Variant chr9-6532477-G-A is described in ClinVar as Benign. ClinVar VariationId is 367162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 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.*540C>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.*540C>T		3_prime_UTR	Exon 25 of 25	ENSP00000370737.4	P23378
	GLDC	ENST00000638233.1	TSL:1	n.2038C>T		non_coding_transcript_exon	Exon 11 of 11
	GLDC	ENST00000920236.1		c.*540C>T		3_prime_UTR	Exon 25 of 25	ENSP00000590295.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107145 AN: 151230 Hom.: 38254 Cov.: 29

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.629 AC: 2041 AN: 3246 Hom.: 673 Cov.: 0 AF XY: 0.628 AC XY: 1092 AN XY: 1738

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.716 AC: 388 AN: 542

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2 AN: 8

East Asian (EAS) AF: 1.00 AC: 32 AN: 32

South Asian (SAS) AF: 0.579 AC: 161 AN: 278

European-Finnish (FIN) AF: 0.725 AC: 309 AN: 426

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.585 AC: 1093 AN: 1868

Other (OTH) AF: 0.628 AC: 54 AN: 86

GnomAD4 genome AF: 0.709 AC: 107227 AN: 151338 Hom.: 38283 Cov.: 29 AF XY: 0.715 AC XY: 52828 AN XY: 73900

African (AFR) AF: 0.700 AC: 28790 AN: 41152

American (AMR) AF: 0.756 AC: 11522 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3466

East Asian (EAS) AF: 0.971 AC: 5007 AN: 5158

South Asian (SAS) AF: 0.722 AC: 3453 AN: 4784

European-Finnish (FIN) AF: 0.765 AC: 7954 AN: 10396

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46127 AN: 67856

Other (OTH) AF: 0.680 AC: 1420 AN: 2088

Alfa AF: 0.688 Hom.: 122638

Bravo AF: 0.706

Asia WGS AF: 0.826 AC: 2873 AN: 3478

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	-0.90
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		0.69
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: rs7848919; hg19: chr9-6532477;