17-19648981-GAA-CAG

Variant names:

• chr17-19648981-GAA-CAG
• NM_000382.3:c.10_12delGAAinsCAG
• ALDH3A2 p.Glu4Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000382.3(ALDH3A2):​c.10_12delGAAinsCAG​(p.Glu4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. E4K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALDH3A2 NM_000382.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 0 publications found

Genes affected

ALDH3A2 (HGNC:403): (aldehyde dehydrogenase 3 family member A2) Aldehyde dehydrogenase isozymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This gene product catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. Mutations in the gene cause Sjogren-Larsson syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ALDH3A2 Gene-Disease associations (from GenCC):

• Sjogren-Larsson syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Myriad Women's Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000382.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	NM_000382.3	MANE Select	c.10_12delGAAinsCAG	p.Glu4Gln	missense	N/A	NP_000373.1	P51648-1
	ALDH3A2	NM_001031806.2		c.10_12delGAAinsCAG	p.Glu4Gln	missense	N/A	NP_001026976.1	P51648-2
	ALDH3A2	NM_001369136.1		c.10_12delGAAinsCAG	p.Glu4Gln	missense	N/A	NP_001356065.1	P51648-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.10_12delGAAinsCAG	p.Glu4Gln	missense	N/A	ENSP00000176643.6	P51648-1
	ALDH3A2	ENST00000339618.8	TSL:1	c.10_12delGAAinsCAG	p.Glu4Gln	missense	N/A	ENSP00000345774.4	P51648-2
	ALDH3A2	ENST00000671878.1		c.10_12delGAAinsCAG	p.Glu4Gln	missense	N/A	ENSP00000500516.1	A0A5F9ZHN9

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.091

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-19552294;