rs11188410

Variant names:

• chr10-95636804-C-A
• rs11188410
• NM_002860.4:c.558+289G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-95636804-C-A
• chr10-95636804-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002860.4(ALDH18A1):​c.558+289G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 152,276 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (297 hom., cov: 33)
• Consequence: ALDH18A1 NM_002860.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00300
• Publications: 0 publications found

Genes affected

ALDH18A1 (HGNC:9722): (aldehyde dehydrogenase 18 family member A1) This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

ALDH18A1 Gene-Disease associations (from GenCC):

• cutis laxa, autosomal dominant 3

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ALDH18A1-related de Barsy syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive complex spastic paraplegia type 9B

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• P5CS deficiency

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• hereditary spastic paraplegia 9A

  Inheritance: AD, SD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• autosomal dominant complex spastic paraplegia type 9B

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant cutis laxa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-95636804-C-A is Benign according to our data. Variant chr10-95636804-C-A is described in ClinVar as Benign. ClinVar VariationId is 669715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002860.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH18A1	NM_002860.4	MANE Select	c.558+289G>T		intron	N/A	NP_002851.2
	ALDH18A1	NM_001323413.2		c.558+289G>T		intron	N/A	NP_001310342.1
	ALDH18A1	NM_001323414.2		c.558+289G>T		intron	N/A	NP_001310343.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH18A1	ENST00000371224.7	TSL:1 MANE Select	c.558+289G>T		intron	N/A	ENSP00000360268.2
	ALDH18A1	ENST00000371221.3	TSL:1	c.558+289G>T		intron	N/A	ENSP00000360265.3

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9032 AN: 152158 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0593 AC: 9034 AN: 152276 Hom.: 297 Cov.: 33 AF XY: 0.0601 AC XY: 4476 AN XY: 74462

African (AFR) AF: 0.0477 AC: 1983 AN: 41552

American (AMR) AF: 0.0578 AC: 884 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 80 AN: 3472

East Asian (EAS) AF: 0.0449 AC: 233 AN: 5192

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4824

European-Finnish (FIN) AF: 0.0764 AC: 811 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0641 AC: 4362 AN: 68008

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0564 Hom.: 320

Bravo AF: 0.0560

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.83
DANN	Benign	0.47
PhyloP100		0.0030
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: rs11188410; hg19: chr10-97396561;