rs1266949739

Variant names:

• chr3-126131415-C-A
• NM_012190.4:c.1592G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-126131415-C-A
• chr3-126131415-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012190.4(ALDH1L1):​c.1592G>T​(p.Arg531Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ALDH1L1 NM_012190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78

Genes affected

ALDH1L1 (HGNC:3978): (aldehyde dehydrogenase 1 family member L1) The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1592G>T	p.Arg531Leu	missense_variant	Exon 13 of 23	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1592G>T	p.Arg531Leu	missense_variant	Exon 13 of 23	1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456598 Hom.: 0 Cov.: 65 AF XY: 0.00000138 AC XY: 1 AN XY: 723634

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;D;.;D
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	D;.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.94	D;D;D;D
MetaSVM	Uncertain	0.017	D
MutationAssessor	Pathogenic	2.9	.;M;.;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.1	D;D;D;D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;.;D
Vest4		0.91
MutPred		0.80		.;Loss of catalytic residue at R531 (P = 0.0053);.;Loss of catalytic residue at R531 (P = 0.0053);
MVP		0.81
MPC		0.56
ClinPred		1.0	D
GERP RS		1.2
Varity_R		0.89
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-125850258;