chr11-67663225-G-A

Position:

• chr11-67663225-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393402.2(ALDH3B2):​c.1148C>T​(p.Thr383Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: ALDH3B2 NM_001393402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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]

ACMG classification

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=0.26035145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B2	NM_001393402.2	c.1148C>T	p.Thr383Ile	missense_variant	10/10	ENST00000673966.2	NP_001380331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3B2	ENST00000673966.2	c.1148C>T	p.Thr383Ile	missense_variant	10/10		NM_001393402.2	ENSP00000501254.1
ALDH3B2	ENST00000530069.6	c.1148C>T	p.Thr383Ile	missense_variant	10/10	1		ENSP00000431595.1
ALDH3B2	ENST00000349015.7	c.1148C>T	p.Thr383Ile	missense_variant	10/10	5		ENSP00000255084.3
ALDH3B2	ENST00000531248.1	c.333C>T	p.His111His	synonymous_variant	3/3	5		ENSP00000435476.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.1148C>T (p.T383I) alteration is located in exon 10 (coding exon 8) of the ALDH3B2 gene. This alteration results from a C to T substitution at nucleotide position 1148, causing the threonine (T) at amino acid position 383 to be replaced by an isoleucine (I). 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	0.13
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Uncertain	0.97
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.42	.;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.98	D;D
Vest4		0.13
MutPred		0.21		Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);
MVP		0.79
MPC		0.23
ClinPred		0.60	D
GERP RS		0.75
Varity_R		0.059
gMVP		0.68

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.

Other links and lift over

hg19: chr11-67430696;