chr11-67664416-C-T

Variant names:

• chr11-67664416-C-T
• rs147016371
• NM_001393402.2:c.853G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393402.2(ALDH3B2):​c.853G>A​(p.Ala285Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: ALDH3B2 NM_001393402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12542233).

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.853G>A	p.Ala285Thr	missense	Exon 8 of 10	NP_001380331.1	P48448
	ALDH3B2	NM_001031615.3		c.853G>A	p.Ala285Thr	missense	Exon 8 of 10	NP_001026786.3	P48448
	ALDH3B2	NM_001354345.3		c.853G>A	p.Ala285Thr	missense	Exon 9 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.853G>A	p.Ala285Thr	missense	Exon 8 of 10	ENSP00000501254.1	P48448
	ALDH3B2	ENST00000530069.6	TSL:1	c.853G>A	p.Ala285Thr	missense	Exon 8 of 10	ENSP00000431595.1	P48448
	ALDH3B2	ENST00000349015.7	TSL:5	c.853G>A	p.Ala285Thr	missense	Exon 8 of 10	ENSP00000255084.3	P48448

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000231 AC: 58 AN: 251342 AF XY: 0.000250

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000177 AC: 259 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 146 AN XY: 727234

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00199 AC: 52 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000158 AC: 176 AN: 1112000

Other (OTH) AF: 0.000348 AC: 21 AN: 60396

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

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

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000376 Hom.: 0

Bravo AF: 0.000166

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000436

EpiControl AF: 0.000593

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	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.29
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.032	D
Polyphen		0.94	P
Vest4		0.31
MVP		0.84
MPC		0.24
ClinPred		0.074	T
GERP RS		2.8
Varity_R		0.28
gMVP		0.64
Mutation Taster		=82/18	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: rs147016371; hg19: chr11-67431887; COSMIC: COSV62427730; COSMIC: COSV62427730;