rs764417585

Variant names:

• chr5-126577199-G-A
• NM_001182.5:c.530C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-126577199-G-A
• chr5-126577199-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001182.5(ALDH7A1):​c.530C>T​(p.Ala177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A177E) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALDH7A1 NM_001182.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr5-126577199-G-T is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.16444981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH7A1	NM_001182.5	c.530C>T	p.Ala177Val	missense_variant	Exon 6 of 18	ENST00000409134.8	NP_001173.2
ALDH7A1	NM_001201377.2	c.446C>T	p.Ala149Val	missense_variant	Exon 6 of 18		NP_001188306.1
ALDH7A1	NM_001202404.2	c.530C>T	p.Ala177Val	missense_variant	Exon 6 of 16		NP_001189333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8	c.530C>T	p.Ala177Val	missense_variant	Exon 6 of 18	1	NM_001182.5	ENSP00000387123.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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: 8.99e-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	0.091
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.8
DANN	Benign	0.71
DEOGEN2	Benign	0.0072	T;T;T;.;T;.;.;.;T;T;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.28	.;N;.;.;.;.;.;N;.;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.070	.;N;.;.;.;.;.;N;.;.;N;.
REVEL	Benign	0.18
Sift	Benign	0.35	.;T;.;.;.;.;.;T;.;.;T;.
Sift4G	Benign	0.32	.;T;.;.;.;.;.;T;.;T;.;.
Polyphen		0.0080	.;B;.;.;.;.;.;.;.;.;.;.
Vest4		0.26, 0.30, 0.25
MutPred		0.41		Loss of disorder (P = 0.0712);Loss of disorder (P = 0.0712);Loss of disorder (P = 0.0712);Loss of disorder (P = 0.0712);.;.;.;Loss of disorder (P = 0.0712);.;Loss of disorder (P = 0.0712);.;.;
MVP		0.84
MPC		0.15
ClinPred		0.30	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.55

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: chr5-125912891;