11-67665293-C-A

Variant names:

• chr11-67665293-C-A
• rs768579203
• NM_001393402.2:c.698G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393402.2(ALDH3B2):​c.698G>T​(p.Arg233Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,605,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R233H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ALDH3B2 NM_001393402.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11340016).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B2	NM_001393402.2	MANE Select	c.698G>T	p.Arg233Leu	missense	Exon 7 of 10	NP_001380331.1	P48448
	ALDH3B2	NM_001031615.3		c.698G>T	p.Arg233Leu	missense	Exon 7 of 10	NP_001026786.3	P48448
	ALDH3B2	NM_001354345.3		c.698G>T	p.Arg233Leu	missense	Exon 8 of 11	NP_001341274.2	P48448

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B2	ENST00000673966.2	MANE Select	c.698G>T	p.Arg233Leu	missense	Exon 7 of 10	ENSP00000501254.1	P48448
	ALDH3B2	ENST00000530069.6	TSL:1	c.698G>T	p.Arg233Leu	missense	Exon 7 of 10	ENSP00000431595.1	P48448
	ALDH3B2	ENST00000349015.7	TSL:5	c.698G>T	p.Arg233Leu	missense	Exon 7 of 10	ENSP00000255084.3	P48448

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453628 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722504

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25406

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 84814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107372

Other (OTH) AF: 0.00 AC: 0 AN: 60038

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41482

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.6
DANN	Benign	0.84
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.78	N
PhyloP100		-0.087
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.21
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.63		Loss of disorder (P = 0.0461)
MVP		0.41
MPC		0.25
ClinPred		0.13	T
GERP RS		-4.5
PromoterAI		0.0028	Neutral
Varity_R		0.25
gMVP		0.71
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs768579203; hg19: chr11-67432764;