chr1-165668955-T-C

Variant names:

• chr1-165668955-T-C
• rs148959290
• NM_000696.4:c.1178A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000696.4(ALDH9A1):​c.1178A>G​(p.Asp393Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,610,724 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (2 hom.)
• Consequence: ALDH9A1 NM_000696.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 2 publications found

Genes affected

ALDH9A1 (HGNC:412): (aldehyde dehydrogenase 9 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. It has a high activity for oxidation of gamma-aminobutyraldehyde and other amino aldehydes. The enzyme catalyzes the dehydrogenation of gamma-aminobutyraldehyde to gamma-aminobutyric acid (GABA). This isozyme is a tetramer of identical 54-kD subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000696.4. 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
	ALDH9A1	NM_000696.4	MANE Select	c.1178A>G	p.Asp393Gly	missense	Exon 8 of 11	NP_000687.3
	ALDH9A1	NM_001365774.2		c.896A>G	p.Asp299Gly	missense	Exon 8 of 11	NP_001352703.1	P49189-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH9A1	ENST00000354775.5	TSL:1 MANE Select	c.1178A>G	p.Asp393Gly	missense	Exon 8 of 11	ENSP00000346827.4	P49189-3
	ALDH9A1	ENST00000865475.1		c.1175A>G	p.Asp392Gly	missense	Exon 8 of 11	ENSP00000535534.1
	ALDH9A1	ENST00000865474.1		c.1148A>G	p.Asp383Gly	missense	Exon 8 of 11	ENSP00000535533.1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000323 AC: 81 AN: 250782 AF XY: 0.000251

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000600

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000669 AC: 975 AN: 1458402 Hom.: 2 Cov.: 29 AF XY: 0.000641 AC XY: 465 AN XY: 725770

African (AFR) AF: 0.0000599 AC: 2 AN: 33378

American (AMR) AF: 0.000112 AC: 5 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86104

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000836 AC: 927 AN: 1109066

Other (OTH) AF: 0.000564 AC: 34 AN: 60312

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27 AN XY: 74484

African (AFR) AF: 0.000120 AC: 5 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000615 Hom.: 0

Bravo AF: 0.000419

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000321 AC: 39

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000764

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.8
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.15
Sift	Benign	0.73	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.63
MPC		0.18
ClinPred		0.0087	T
GERP RS		-0.11
gMVP		0.67
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.40		Position offset: -29

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148959290; hg19: chr1-165638192; COSMIC: COSV105261603; COSMIC: COSV105261603;