17-19648757-C-G

Variant names:

• chr17-19648757-C-G
• rs996835923
• NM_000382.3:c.-215C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000382.3(ALDH3A2):​c.-215C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 489,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: ALDH3A2 NM_000382.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• 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: Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.-215C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_000373.1	P51648-1
	ALDH3A2	NM_000382.3	MANE Select	c.-215C>G		5_prime_UTR	Exon 1 of 10	NP_000373.1	P51648-1
	ALDH3A2	NM_001031806.2		c.-215C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001026976.1	P51648-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.-215C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000176643.6	P51648-1
	ALDH3A2	ENST00000339618.8	TSL:1	c.-215C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000345774.4	P51648-2
	ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.-215C>G		5_prime_UTR	Exon 1 of 10	ENSP00000176643.6	P51648-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000204 AC: 1 AN: 489792 Hom.: 0 Cov.: 6 AF XY: 0.00000392 AC XY: 1 AN XY: 255078

African (AFR) AF: 0.00 AC: 0 AN: 13494

American (AMR) AF: 0.00 AC: 0 AN: 20826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14106

East Asian (EAS) AF: 0.0000326 AC: 1 AN: 30628

South Asian (SAS) AF: 0.00 AC: 0 AN: 47954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 304470

Other (OTH) AF: 0.00 AC: 0 AN: 27292

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.48
PhyloP100		0.61
PromoterAI		-0.043	Neutral

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

Other links and lift over

dbSNP: rs996835923; hg19: chr17-19552070;