NM_003888.4:c.1521G>A

Variant names:

• chr15-57955233-C-T
• rs751479287
• NM_003888.4:c.1521G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003888.4(ALDH1A2):​c.1521G>A​(p.Lys507Lys) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDH1A2 NM_003888.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

Genes affected

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.1521G>A	p.Lys507Lys	synonymous_variant	Exon 13 of 13	ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.1458G>A	p.Lys486Lys	synonymous_variant	Exon 14 of 14		NP_001193826.1
ALDH1A2	NM_170696.3	c.1407G>A	p.Lys469Lys	synonymous_variant	Exon 12 of 12		NP_733797.1
ALDH1A2	NM_170697.3	c.1233G>A	p.Lys411Lys	synonymous_variant	Exon 11 of 11		NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1521G>A	p.Lys507Lys	synonymous_variant	Exon 13 of 13	1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs751479287; hg19: chr15-58247431;