chr11-68026041-C-A

Variant names:

• chr11-68026041-C-A
• rs2286163
• NM_000694.4:c.1149C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000694.4(ALDH3B1):​c.1149C>A​(p.Ser383Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ALDH3B1 NM_000694.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 28 publications found

Genes affected

ALDH3B1 (HGNC:410): (aldehyde dehydrogenase 3 family member B1) This gene encodes a member of the aldehyde dehydrogenase protein family. Aldehyde dehydrogenases are a family of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The encoded protein is able to oxidize long-chain fatty aldehydes in vitro, and may play a role in protection from oxidative stress. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GLTC1 (HGNC:56861):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B1	NM_000694.4	MANE Select	c.1149C>A	p.Ser383Arg	missense	Exon 9 of 10	NP_000685.1
	ALDH3B1	NM_001161473.3		c.1149C>A	p.Ser383Arg	missense	Exon 9 of 10	NP_001154945.1
	ALDH3B1	NM_001030010.3		c.1038C>A	p.Ser346Arg	missense	Exon 8 of 9	NP_001025181.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B1	ENST00000342456.11	TSL:1 MANE Select	c.1149C>A	p.Ser383Arg	missense	Exon 9 of 10	ENSP00000473990.2
	ALDH3B1	ENST00000614849.4	TSL:1	c.1149C>A	p.Ser383Arg	missense	Exon 9 of 10	ENSP00000478486.1
	ALDH3B1	ENST00000617288.4	TSL:1	c.1038C>A	p.Ser346Arg	missense	Exon 8 of 9	ENSP00000481604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455642 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723740

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39296

South Asian (SAS) AF: 0.00 AC: 0 AN: 84920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109012

Other (OTH) AF: 0.00 AC: 0 AN: 60126

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 16703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	20
DANN	Benign	0.75
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.89	D
PhyloP100		-1.6
PrimateAI	Benign	0.48	T
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.91
MVP		0.57
GERP RS		-2.1
Varity_R		0.90
gMVP		0.93
Mutation Taster		=76/24	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: rs2286163; hg19: chr11-67793509;