rs1262777866

Variant names:

• chr6-24495143-G-T
• rs1262777866
• NM_001080.3:c.147G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24495143-G-T
• chr6-24495143-G-A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001080.3(ALDH5A1):​c.147G>T​(p.Gly49Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000565 in 1,416,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (1 hom.)
• Consequence: ALDH5A1 NM_001080.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250
• Publications: 0 publications found

Genes affected

ALDH5A1 (HGNC:408): (aldehyde dehydrogenase 5 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GPLD1 (HGNC:4459): (glycosylphosphatidylinositol specific phospholipase D1) Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-24495143-G-T is Benign according to our data. Variant chr6-24495143-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 459980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.025 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080.3. 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
	ALDH5A1	NM_001080.3	MANE Select	c.147G>T	p.Gly49Gly	synonymous	Exon 1 of 10	NP_001071.1	X5DQN2
	ALDH5A1	NM_170740.1		c.147G>T	p.Gly49Gly	synonymous	Exon 1 of 11	NP_733936.1	X5D299
	ALDH5A1	NM_001368954.1		c.147G>T	p.Gly49Gly	synonymous	Exon 1 of 9	NP_001355883.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH5A1	ENST00000357578.8	TSL:1 MANE Select	c.147G>T	p.Gly49Gly	synonymous	Exon 1 of 10	ENSP00000350191.3	P51649-1
	ALDH5A1	ENST00000348925.2	TSL:1	c.147G>T	p.Gly49Gly	synonymous	Exon 1 of 11	ENSP00000314649.3	P51649-2
	ALDH5A1	ENST00000859838.1		c.147G>T	p.Gly49Gly	synonymous	Exon 1 of 11	ENSP00000529897.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151788 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000108 AC: 5 AN: 46482 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000590

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000554 AC: 7 AN: 1264334 Hom.: 1 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 620900

African (AFR) AF: 0.00 AC: 0 AN: 24972

American (AMR) AF: 0.000325 AC: 6 AN: 18480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20012

East Asian (EAS) AF: 0.00 AC: 0 AN: 27608

South Asian (SAS) AF: 0.00 AC: 0 AN: 61766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3652

European-Non Finnish (NFE) AF: 9.76e-7 AC: 1 AN: 1024398

Other (OTH) AF: 0.00 AC: 0 AN: 52088

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151788 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74134

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67870

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Succinate-semialdehyde dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		-0.025
PromoterAI		0.028	Neutral

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: rs1262777866; hg19: chr6-24495371;