11-67665381-T-A

Position:

• chr11-67665381-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001393402.2(ALDH3B2):​c.610A>T​(p.Ile204Phe) 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 pathogenic 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: 1.70

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B2	NM_001393402.2	c.610A>T	p.Ile204Phe	missense_variant	7/10	ENST00000673966.2	NP_001380331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3B2	ENST00000673966.2	c.610A>T	p.Ile204Phe	missense_variant	7/10		NM_001393402.2	ENSP00000501254	P1
ALDH3B2	ENST00000530069.6	c.610A>T	p.Ile204Phe	missense_variant	7/10	1		ENSP00000431595	P1
ALDH3B2	ENST00000349015.7	c.610A>T	p.Ile204Phe	missense_variant	7/10	5		ENSP00000255084	P1
ALDH3B2	ENST00000534425.6	n.1041A>T		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 94

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

Jun 06, 2023

The c.610A>T (p.I204F) alteration is located in exon 7 (coding exon 5) of the ALDH3B2 gene. This alteration results from a A to T substitution at nucleotide position 610, causing the isoleucine (I) at amino acid position 204 to be replaced by a phenylalanine (F). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	4.2	H;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.98	D;D
Vest4		0.81
MutPred		0.78		Loss of MoRF binding (P = 0.1164);Loss of MoRF binding (P = 0.1164);
MVP		0.86
MPC		0.94
ClinPred		1.0	D
GERP RS		3.0
Varity_R		0.95
gMVP		0.86

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: chr11-67432852;