Genetic Variant NM_001393402.2:c.694G>A (chr11-67665297-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_001393402.2(ALDH3B2):c.694G>A(p.Asp232Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,607,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

ALDH3B2
NM_001393402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0920

Publications

0 publications found

Variant links:

Genes affected

ALDH3B2 (HGNC:411): (aldehyde dehydrogenase 3 family member B2) This gene encodes a member of the aldehyde dehydrogenase family, a group of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The gene of this particular family member is over 10 kb in length. Altered methylation patterns at this locus have been observed in spermatozoa derived from patients exhibiting reduced fecundity. [provided by RefSeq, Aug 2017]

ALDH3B2 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 (MetaRNN=0.0648092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393402.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDH3B2	NM_001393402.2	MANE Select	c.694G>A	p.Asp232Asn	missense	Exon 7 of 10	NP_001380331.1	P48448
ALDH3B2	NM_001031615.3		c.694G>A	p.Asp232Asn	missense	Exon 7 of 10	NP_001026786.3	P48448
ALDH3B2	NM_001354345.3		c.694G>A	p.Asp232Asn	missense	Exon 8 of 11	NP_001341274.2	P48448

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDH3B2	ENST00000673966.2	MANE Select	c.694G>A	p.Asp232Asn	missense	Exon 7 of 10	ENSP00000501254.1	P48448
ALDH3B2	ENST00000530069.6	TSL:1	c.694G>A	p.Asp232Asn	missense	Exon 7 of 10	ENSP00000431595.1	P48448
ALDH3B2	ENST00000349015.7	TSL:5	c.694G>A	p.Asp232Asn	missense	Exon 7 of 10	ENSP00000255084.3	P48448

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000651

AC:

AN:

245848

AF XY:

0.0000527

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1455402

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

723608

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33374

American (AMR)

AF:

0.000316

AC:

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.0000391

AC:

AN:

25578

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000352

AC:

AN:

85206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000262

AC:

AN:

1108306

Other (OTH)

AF:

0.0000998

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000987

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.073

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.80

M_CAP

Benign

0.054

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

PhyloP100

0.092

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

REVEL

Benign

0.095

Sift

Benign

0.11

Sift4G

Benign

0.15

Polyphen

0.014

Vest4

0.15

MVP

0.63

MPC

0.20

ClinPred

0.047

GERP RS

-3.2

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.13

gMVP

0.63

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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