chr17-19740386-C-T

Variant names:

• chr17-19740386-C-T
• rs142078447
• NM_000691.5:c.899G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000691.5(ALDH3A1):​c.899G>A​(p.Gly300Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,614,114 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (74 hom.)
• Consequence: ALDH3A1 NM_000691.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.00
• Publications: 12 publications found

Genes affected

ALDH3A1 (HGNC:405): (aldehyde dehydrogenase 3 family member A1) Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009444386).
• BP6: Variant 17-19740386-C-T is Benign according to our data. Variant chr17-19740386-C-T is described in ClinVar as Benign. ClinVar VariationId is 778684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000691.5. 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
	ALDH3A1	NM_000691.5	MANE Select	c.899G>A	p.Gly300Asp	missense	Exon 7 of 11	NP_000682.3
	ALDH3A1	NM_001135167.1		c.899G>A	p.Gly300Asp	missense	Exon 7 of 11	NP_001128639.1	P30838
	ALDH3A1	NM_001135168.1		c.899G>A	p.Gly300Asp	missense	Exon 6 of 10	NP_001128640.1	P30838

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A1	ENST00000225740.11	TSL:1 MANE Select	c.899G>A	p.Gly300Asp	missense	Exon 7 of 11	ENSP00000225740.6	P30838
	ALDH3A1	ENST00000457500.6	TSL:1	c.899G>A	p.Gly300Asp	missense	Exon 6 of 10	ENSP00000411821.2	P30838
	ALDH3A1	ENST00000905965.1		c.920G>A	p.Gly307Asp	missense	Exon 7 of 11	ENSP00000576024.1

Frequencies

GnomAD3 genomes AF: 0.00622 AC: 947 AN: 152170 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00939

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00675 AC: 1696 AN: 251424 AF XY: 0.00754

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00842 AC: 12309 AN: 1461826 Hom.: 74 Cov.: 30 AF XY: 0.00845 AC XY: 6147 AN XY: 727216

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.00465 AC: 208 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 302 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00636 AC: 549 AN: 86256

European-Finnish (FIN) AF: 0.00122 AC: 65 AN: 53364

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.00952 AC: 10586 AN: 1112006

Other (OTH) AF: 0.00848 AC: 512 AN: 60394

GnomAD4 genome AF: 0.00621 AC: 946 AN: 152288 Hom.: 7 Cov.: 32 AF XY: 0.00594 AC XY: 442 AN XY: 74466

African (AFR) AF: 0.00152 AC: 63 AN: 41552

American (AMR) AF: 0.00588 AC: 90 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4828

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00940 AC: 639 AN: 68012

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00817 Hom.: 19

Bravo AF: 0.00663

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00856 AC: 33

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00965 AC: 83

ExAC AF: 0.00728 AC: 884

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0137

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.40
Sift	Benign	0.24	T
Sift4G	Benign	0.45	T
Polyphen		0.015	B
Vest4		0.34
MVP		0.68
MPC		0.65
ClinPred		0.026	T
GERP RS		3.0
Varity_R		0.70
gMVP		0.68
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs142078447; hg19: chr17-19643699; COSMIC: COSV56734758; COSMIC: COSV56734758;