Variant 11-67663252-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393402.2(ALDH3B2):c.1121G>A(p.Arg374His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,613,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

ALDH3B2
NM_001393402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.624

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09203324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B2	NM_001393402.2 linkuse as main transcript	c.1121G>A	p.Arg374His	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.1121G>A	p.Arg374His	missense_variant	10/10		NM_001393402.2	ENSP00000501254.1	P48448
ALDH3B2	ENST00000530069.6 linkuse as main transcript	c.1121G>A	p.Arg374His	missense_variant	10/10	1		ENSP00000431595.1	P48448
ALDH3B2	ENST00000349015.7 linkuse as main transcript	c.1121G>A	p.Arg374His	missense_variant	10/10	5		ENSP00000255084.3	P48448
ALDH3B2	ENST00000531248.1 linkuse as main transcript	c.306G>A	p.Thr102Thr	synonymous_variant	3/3	5		ENSP00000435476.1	H0YEC0

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000240

AC:

AN:

250004

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.000503

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.000822

GnomAD4 exome

AF:

0.000209

AC:

305

AN:

1460810

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

136

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000605

Gnomad4 ASJ exome

AF:

0.000538

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000223

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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

Oct 06, 2021

The c.1121G>A (p.R374H) alteration is located in exon 10 (coding exon 8) of the ALDH3B2 gene. This alteration results from a G to A substitution at nucleotide position 1121, causing the arginine (R) at amino acid position 374 to be replaced by a histidine (H). 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

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.98

D;D

Vest4

0.042

MVP

0.79

MPC

0.24

ClinPred

0.062

GERP RS

-3.2

Varity_R

0.036

gMVP

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over