3-126146923-C-G

Position:

• chr3-126146923-C-G

Variant summary

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

The NM_012190.4(ALDH1L1):​c.988G>C​(p.Val330Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. V330F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDH1L1 NM_012190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1317372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1L1	NM_012190.4	c.988G>C	p.Val330Leu	missense_variant	9/23	ENST00000393434.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.988G>C	p.Val330Leu	missense_variant	9/23	1	NM_012190.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.087	.;.;T;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.67	T;T;.;T;T;.
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;L;.;L;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	.;N;N;N;N;N
REVEL	Benign	0.022
Sift	Uncertain	0.0060	.;D;D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D;D
Polyphen		0.0080	.;.;B;.;B;.
Vest4		0.17
MutPred		0.26		Loss of MoRF binding (P = 0.1405);.;Loss of MoRF binding (P = 0.1405);.;Loss of MoRF binding (P = 0.1405);Loss of MoRF binding (P = 0.1405);
MVP		0.16
MPC		0.18
ClinPred		0.19	T
GERP RS		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs2886059; hg19: chr3-125865766;