NM_001393402.2:c.501C>G

Variant names:

• chr11-67665490-G-C
• rs754993637
• NM_001393402.2:c.501C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001393402.2(ALDH3B2):​c.501C>G​(p.Asp167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,024 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D167A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ALDH3B2 NM_001393402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• 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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

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.501C>G	p.Asp167Glu	missense	Exon 7 of 10	NP_001380331.1	P48448
	ALDH3B2	NM_001031615.3		c.501C>G	p.Asp167Glu	missense	Exon 7 of 10	NP_001026786.3	P48448
	ALDH3B2	NM_001354345.3		c.501C>G	p.Asp167Glu	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.501C>G	p.Asp167Glu	missense	Exon 7 of 10	ENSP00000501254.1	P48448
	ALDH3B2	ENST00000530069.6	TSL:1	c.501C>G	p.Asp167Glu	missense	Exon 7 of 10	ENSP00000431595.1	P48448
	ALDH3B2	ENST00000349015.7	TSL:5	c.501C>G	p.Asp167Glu	missense	Exon 7 of 10	ENSP00000255084.3	P48448

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251362 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461832 Hom.: 0 Cov.: 36 AF XY: 0.0000124 AC XY: 9 AN XY: 727226

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74346

African (AFR) AF: 0.0000724 AC: 3 AN: 41438

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.072
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.075	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.017	D
Polyphen		0.94	P
Vest4		0.72
MutPred		0.77		Gain of sheet (P = 0.0827)
MVP		0.89
MPC		0.53
ClinPred		0.76	D
GERP RS		0.82
PromoterAI		-0.012	Neutral
Varity_R		0.63
gMVP		0.78
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs754993637; hg19: chr11-67432961;