Variant chr2-210195331-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000233710.4(ACADL):c.992A>G(p.Gln331Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000184 in 1,611,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ACADL
ENST00000233710.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17878222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACADL	NM_001608.4 linkuse as main transcript	c.992A>G	p.Gln331Arg	missense_variant	9/11	ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5 linkuse as main transcript	c.929A>G	p.Gln310Arg	missense_variant	9/11		XP_005246574.1
ACADL	XM_047444103.1 linkuse as main transcript	c.569A>G	p.Gln190Arg	missense_variant	9/11		XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ACADL	ENST00000233710.4 linkuse as main transcript	c.992A>G	p.Gln331Arg	missense_variant	9/11	1	NM_001608.4	ENSP00000233710	P1
	ENST00000639259.2 linkuse as main transcript	n.279+23502T>C		intron_variant, non_coding_transcript_variant		5
ACADL	ENST00000652584.1 linkuse as main transcript	n.1220A>G		non_coding_transcript_exon_variant	9/11
	ENST00000412065.1 linkuse as main transcript	n.313-23141T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

250890

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000192

AC:

281

AN:

1459778

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

726290

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000105

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.992A>G (p.Q331R) alteration is located in exon 9 (coding exon 9) of the ACADL gene. This alteration results from a A to G substitution at nucleotide position 992, causing the glutamine (Q) at amino acid position 331 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

M_CAP

Benign

0.043

MetaRNN

Benign

0.18

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

0.48

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.79

REVEL

Uncertain

0.58

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.42

MutPred

0.79

Gain of MoRF binding (P = 0.0202);

MVP

0.96

MPC

0.26

ClinPred

0.040

GERP RS

5.8

Varity_R

0.37

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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