Genetic Variant NM_000382.3:c.-67C>T (chr17-19648905-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000382.3(ALDH3A2):c.-67C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,530,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

ALDH3A2
NM_000382.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.158

Publications

0 publications found

Variant links:

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

ALDH3A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH3A2	NM_000382.3	MANE Select	c.-67C>T	5_prime_UTR	Exon 1 of 10	NP_000373.1	P51648-1
ALDH3A2	NM_001031806.2		c.-67C>T	5_prime_UTR	Exon 1 of 11	NP_001026976.1	P51648-2
ALDH3A2	NM_001369136.1		c.-37-30C>T	intron	N/A	NP_001356065.1	P51648-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.-67C>T	5_prime_UTR	Exon 1 of 10	ENSP00000176643.6	P51648-1
ALDH3A2	ENST00000339618.8	TSL:1	c.-67C>T	5_prime_UTR	Exon 1 of 11	ENSP00000345774.4	P51648-2
ALDH3A2	ENST00000671878.1		c.-67C>T	5_prime_UTR	Exon 1 of 10	ENSP00000500516.1	A0A5F9ZHN9

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000302

AC:

417

AN:

1378530

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

209

AN XY:

678130

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31638

American (AMR)

AF:

0.00

AC:

AN:

35580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25028

East Asian (EAS)

AF:

0.00

AC:

AN:

35958

South Asian (SAS)

AF:

0.00

AC:

AN:

79006

European-Finnish (FIN)

AF:

0.0000489

AC:

AN:

40890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4064

European-Non Finnish (NFE)

AF:

0.000380

AC:

406

AN:

1069254

Other (OTH)

AF:

0.000140

AC:

AN:

57112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000164

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000155

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Sjögren-Larsson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.3

(source)

DANN

Benign

0.69

PhyloP100

0.16

PromoterAI

0.42

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over