Variant 11-67663279-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001393402.2(ALDH3B2):c.1094A>C(p.Tyr365Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALDH3B2
NM_001393402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B2	NM_001393402.2 linkuse as main transcript	c.1094A>C	p.Tyr365Ser	missense_variant	10/10	ENST00000673966.2	NP_001380331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ALDH3B2	ENST00000673966.2 linkuse as main transcript	c.1094A>C	p.Tyr365Ser	missense_variant	10/10		NM_001393402.2	ENSP00000501254.1	P48448
ALDH3B2	ENST00000530069.6 linkuse as main transcript	c.1094A>C	p.Tyr365Ser	missense_variant	10/10	1		ENSP00000431595.1	P48448
ALDH3B2	ENST00000349015.7 linkuse as main transcript	c.1094A>C	p.Tyr365Ser	missense_variant	10/10	5		ENSP00000255084.3	P48448
ALDH3B2	ENST00000531248.1 linkuse as main transcript	c.279A>C	p.Leu93Leu	synonymous_variant	3/3	5		ENSP00000435476.1	H0YEC0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.1094A>C (p.Y365S) alteration is located in exon 10 (coding exon 8) of the ALDH3B2 gene. This alteration results from a A to C substitution at nucleotide position 1094, causing the tyrosine (Y) at amino acid position 365 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.29

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.53

.;T

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.0

D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.85

P;P

Vest4

0.48

MutPred

0.64

Loss of catalytic residue at Y365 (P = 0.0271);Loss of catalytic residue at Y365 (P = 0.0271);

MVP

0.90

MPC

0.63

ClinPred

0.99

GERP RS

2.6

Varity_R

0.42

gMVP

0.90

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over