17-19648599-G-C

Variant names:

• chr17-19648599-G-C
• rs571225645
• ENST00000631291.2:c.-373G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001369137.2(ALDH3A2):​c.-38+334G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 244,030 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (2 hom.)
• Consequence: ALDH3A2 NM_001369137.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-19648599-G-C is Benign according to our data. Variant chr17-19648599-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1343035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00255 (389/152280) while in subpopulation NFE AF = 0.00371 (252/68010). AF 95% confidence interval is 0.00333. There are 3 homozygotes in GnomAd4. There are 186 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369137.2. 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_001369137.2		c.-38+334G>C		intron	N/A	NP_001356066.1	P51648-2
	ALDH3A2	NM_001369138.2		c.-38+334G>C		intron	N/A	NP_001356067.1	P51648-1
	ALDH3A2	NM_001369146.2		c.-38+334G>C		intron	N/A	NP_001356075.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000631291.2	TSL:5	c.-373G>C		5_prime_UTR	Exon 1 of 9	ENSP00000486085.1	J3QRD1
	ALDH3A2	ENST00000626500.2	TSL:5	c.-373G>C		5_prime_UTR	Exon 1 of 4	ENSP00000486283.1	I3L0X1
	ALDH3A2	ENST00000672465.1		c.-38+334G>C		intron	N/A	ENSP00000500517.1	A0A5F9ZHN9

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152162 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00370

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00381 AC: 350 AN: 91750 Hom.: 2 Cov.: 0 AF XY: 0.00346 AC XY: 169 AN XY: 48870

African (AFR) AF: 0.00 AC: 0 AN: 1550

American (AMR) AF: 0.000296 AC: 1 AN: 3378

Ashkenazi Jewish (ASJ) AF: 0.000404 AC: 1 AN: 2476

East Asian (EAS) AF: 0.00 AC: 0 AN: 3636

South Asian (SAS) AF: 0.00 AC: 0 AN: 13258

European-Finnish (FIN) AF: 0.0110 AC: 65 AN: 5916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 386

European-Non Finnish (NFE) AF: 0.00476 AC: 266 AN: 55874

Other (OTH) AF: 0.00322 AC: 17 AN: 5276

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152280 Hom.: 3 Cov.: 33 AF XY: 0.00250 AC XY: 186 AN XY: 74460

African (AFR) AF: 0.000144 AC: 6 AN: 41568

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0110 AC: 117 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00371 AC: 252 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00350 Hom.: 0

Bravo AF: 0.00145

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.55
PhyloP100		-1.9
PromoterAI		-0.052	Neutral
Mutation Taster		=300/0	polymorphism

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: rs571225645; hg19: chr17-19551912;