rs1060502950

Positions:

• chr5-126595120-C-A
• chr5-126595120-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001182.5(ALDH7A1):​c.79G>T​(p.Ala27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ALDH7A1 NM_001182.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

Genes affected

ALDH7A1 (HGNC:877): (aldehyde dehydrogenase 7 family member A1) The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22178185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH7A1	NM_001182.5	c.79G>T	p.Ala27Ser	missense_variant	1/18	ENST00000409134.8	NP_001173.2
ALDH7A1	NM_001202404.2	c.79G>T	p.Ala27Ser	missense_variant	1/16		NP_001189333.2
ALDH7A1	NM_001201377.2	c.-6G>T		5_prime_UTR_variant	1/18		NP_001188306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8	c.79G>T	p.Ala27Ser	missense_variant	1/18	1	NM_001182.5	ENSP00000387123	P4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428958 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 707986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T;T;T;.;T;.;.;.;T;T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.76	.;N;.;.;.;.;.;N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.13	.;N;.;.;.;.;.;N;.;.;N;N
REVEL	Benign	0.28
Sift	Benign	0.48	.;T;.;.;.;.;.;T;.;.;T;T
Sift4G	Benign	0.73	.;T;.;.;.;.;.;T;.;T;.;.
Polyphen		0.0010	.;B;.;.;.;.;.;.;.;.;.;.
Vest4		0.16, 0.21, 0.24
MutPred		0.45		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;Gain of sheet (P = 0.0266);
MVP		0.87
MPC		0.14
ClinPred		0.47	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.096
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-125930812;