2-210195326-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001608.4(ACADL):c.997A>C(p.Lys333Gln) variant causes a missense change. The variant allele was found at a frequency of 0.329 in 1,610,748 control chromosomes in the GnomAD database, including 90,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6325 hom., cov: 32)

Exomes 𝑓: 0.33 ( 84208 hom. )

Consequence

ACADL
NM_001608.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 7.11

Variant links:

Genes affected

ACADL (HGNC:88): (acyl-CoA dehydrogenase long chain) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

ACADL links:

ENSG00000279317 (HGNC:):

ENSG00000279317 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032475889).

BP6

Variant 2-210195326-T-G is Benign according to our data. Variant chr2-210195326-T-G is described in ClinVar as [Benign]. Clinvar id is 1620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADL	NM_001608.4 link	c.997A>C	p.Lys333Gln	missense_variant	Exon 9 of 11	ENST00000233710.4	NP_001599.1	P28330
ACADL	XM_005246517.5 link	c.934A>C	p.Lys312Gln	missense_variant	Exon 9 of 11		XP_005246574.1
ACADL	XM_047444103.1 link	c.574A>C	p.Lys192Gln	missense_variant	Exon 9 of 11		XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACADL	ENST00000233710.4 link	c.997A>C	p.Lys333Gln	missense_variant	Exon 9 of 11	1	NM_001608.4	ENSP00000233710.3	P28330
ACADL	ENST00000652584.1 link	n.1225A>C		non_coding_transcript_exon_variant	Exon 9 of 11
ENSG00000279317	ENST00000412065.1 link	n.313-23146T>G		intron_variant	Intron 1 of 2	4
ENSG00000279317	ENST00000639259.2 link	n.279+23497T>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41476

AN:

152014

Hom.:

6324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.301

AC:

75355

AN:

250752

Hom.:

11986

AF XY:

0.306

AC XY:

41490

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.335

AC:

488328

AN:

1458618

Hom.:

84208

Cov.:

AF XY:

0.335

AC XY:

242788

AN XY:

725766

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.273

AC:

41472

AN:

152130

Hom.:

6325

Cov.:

AF XY:

0.271

AC XY:

20119

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.326

Hom.:

20156

Bravo

AF:

0.260

TwinsUK

AF:

0.350

AC:

1297

ALSPAC

AF:

0.364

AC:

1402

ESP6500AA

AF:

0.150

AC:

661

ESP6500EA

AF:

0.341

AC:

2936

ExAC

AF:

0.301

AC:

36504

Asia WGS

AF:

0.241

AC:

838

AN:

3478

EpiCase

AF:

0.336

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Apr 11, 2014

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.87

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.6

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.64

Sift

Benign

0.051

Sift4G

Benign

0.071

Polyphen

0.98

Vest4

0.26

MPC

0.85

ClinPred

0.014

GERP RS

5.8

Varity_R

0.63

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over