NM_000696.4:c.739C>G

Variant names:

• chr1-165680537-G-C
• NM_000696.4:c.739C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000696.4(ALDH9A1):​c.739C>G​(p.Pro247Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDH9A1 NM_000696.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.739C>G	p.Pro247Ala	missense	Exon 5 of 11	NP_000687.3
	ALDH9A1	NM_001365774.2		c.457C>G	p.Pro153Ala	missense	Exon 5 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.739C>G	p.Pro247Ala	missense	Exon 5 of 11	ENSP00000346827.4	P49189-3
	ALDH9A1	ENST00000865475.1		c.736C>G	p.Pro246Ala	missense	Exon 5 of 11	ENSP00000535534.1
	ALDH9A1	ENST00000865474.1		c.709C>G	p.Pro237Ala	missense	Exon 5 of 11	ENSP00000535533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.087
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.095
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.20	D
PhyloP100		7.7
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.036	D
Polyphen		0.14	B
Vest4		0.36
MVP		0.83
MPC		0.15
ClinPred		0.62	D
GERP RS		3.7
gMVP		0.53
Mutation Taster		=72/28	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

hg19: chr1-165649774;