chr17-19648739-T-C

Variant names:

• chr17-19648739-T-C
• rs114897153
• ENST00000672357.1:c.-142T>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.-37-196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 599,782 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (15 hom.)
• Consequence: ALDH3A2 NM_001369137.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.611
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-19648739-T-C is Benign according to our data. Variant chr17-19648739-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1326534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1963/152312) while in subpopulation AFR AF = 0.0438 (1823/41582). AF 95% confidence interval is 0.0422. There are 50 homozygotes in GnomAd4. There are 945 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 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.-37-196T>C		intron	N/A	NP_001356066.1	P51648-2
	ALDH3A2	NM_001369138.2		c.-37-196T>C		intron	N/A	NP_001356067.1	P51648-1
	ALDH3A2	NM_001369146.2		c.-37-196T>C		intron	N/A	NP_001356075.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000672357.1		c.-142T>C		5_prime_UTR	Exon 1 of 11	ENSP00000500092.1	P51648-1
	ALDH3A2	ENST00000631291.2	TSL:5	c.-233T>C		5_prime_UTR	Exon 1 of 9	ENSP00000486085.1	J3QRD1
	ALDH3A2	ENST00000626500.2	TSL:5	c.-233T>C		5_prime_UTR	Exon 1 of 4	ENSP00000486283.1	I3L0X1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1959 AN: 152196 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00192 AC: 859 AN: 447470 Hom.: 15 Cov.: 5 AF XY: 0.00165 AC XY: 386 AN XY: 233780

African (AFR) AF: 0.0448 AC: 553 AN: 12340

American (AMR) AF: 0.00343 AC: 64 AN: 18684

Ashkenazi Jewish (ASJ) AF: 0.00262 AC: 35 AN: 13338

East Asian (EAS) AF: 0.00 AC: 0 AN: 29762

South Asian (SAS) AF: 0.0000869 AC: 4 AN: 46014

European-Finnish (FIN) AF: 0.0000356 AC: 1 AN: 28078

Middle Eastern (MID) AF: 0.00312 AC: 6 AN: 1922

European-Non Finnish (NFE) AF: 0.000386 AC: 105 AN: 271786

Other (OTH) AF: 0.00356 AC: 91 AN: 25546

GnomAD4 genome AF: 0.0129 AC: 1963 AN: 152312 Hom.: 50 Cov.: 33 AF XY: 0.0127 AC XY: 945 AN XY: 74476

African (AFR) AF: 0.0438 AC: 1823 AN: 41582

American (AMR) AF: 0.00496 AC: 76 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68008

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00874 Hom.: 1

Bravo AF: 0.0143

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.61
PromoterAI		-0.030	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: rs114897153; hg19: chr17-19552052;