chr17-19648987-C-T

Variant names:

• chr17-19648987-C-T
• rs1468417827
• NM_000382.3:c.16C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001369148.2(ALDH3A2):​c.-673C>T 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 0.00000883 in 1,586,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: ALDH3A2 NM_001369148.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.259
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369148.2. 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_000382.3	MANE Select	c.16C>T	p.Arg6Trp	missense	Exon 1 of 10	NP_000373.1	P51648-1
	ALDH3A2	NM_001369148.2		c.-673C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_001356077.1
	ALDH3A2	NM_001031806.2		c.16C>T	p.Arg6Trp	missense	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.16C>T	p.Arg6Trp	missense	Exon 1 of 10	ENSP00000176643.6	P51648-1
	ALDH3A2	ENST00000339618.8	TSL:1	c.16C>T	p.Arg6Trp	missense	Exon 1 of 11	ENSP00000345774.4	P51648-2
	ALDH3A2	ENST00000630662.2	TSL:5	c.-966C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000487353.1	A0A0D9SGC3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000101 AC: 2 AN: 197790 AF XY: 0.00000933

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000237

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000907 AC: 13 AN: 1433856 Hom.: 0 Cov.: 30 AF XY: 0.0000113 AC XY: 8 AN XY: 710698

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.00 AC: 0 AN: 40242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 38744

South Asian (SAS) AF: 0.00 AC: 0 AN: 82348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5334

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1099170

Other (OTH) AF: 0.00 AC: 0 AN: 59264

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.0097
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.26
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.11
MutPred		0.51		Loss of disorder (P = 0.0162)
MVP		0.97
MPC		0.61
ClinPred		0.94	D
GERP RS		4.3
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.33
Mutation Taster		=72/28	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: rs1468417827; hg19: chr17-19552300; COSMIC: COSV105043826; COSMIC: COSV105043826;