3-132559005-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_032169.5(ACAD11):c.2309G>A(p.Arg770Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000762 in 1,613,646 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (3 hom.)
• Consequence: ACAD11 NM_032169.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07

Genes affected

ACAD11 (HGNC:30211): (acyl-CoA dehydrogenase family member 11) This gene encodes an acyl-CoA dehydrogenase enzyme with a preference for carbon chain lengths between 20 and 26. Naturally occurring read-through transcription occurs between the upstream gene NPHP3 (nephronophthisis 3 (adolescent)) and this gene. [provided by RefSeq, Aug 2015]

NPHP3-ACAD11 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068439543).
• BP6: Variant 3-132559005-C-T is Benign according to our data. Variant chr3-132559005-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2492970.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAD11	NM_032169.5	c.2309G>A	p.Arg770Gln	missense_variant	20/20	ENST00000264990.11
NPHP3-ACAD11	NR_037804.1	n.6921G>A		non_coding_transcript_exon_variant	45/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAD11	ENST00000264990.11	c.2309G>A	p.Arg770Gln	missense_variant	20/20	1	NM_032169.5	P1
ACAD11	ENST00000485198.5	c.*790G>A		3_prime_UTR_variant, NMD_transcript_variant	18/18	1
ACAD11	ENST00000469042.5	n.3095G>A		non_coding_transcript_exon_variant	18/18	2
ACAD11	ENST00000496418.5	n.2817G>A		non_coding_transcript_exon_variant	19/19	2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000148 AC: 37 AN: 250846 Hom.: 1 AF XY: 0.000133 AC XY: 18 AN XY: 135568

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000725 AC: 106 AN: 1461410 Hom.: 3 Cov.: 30 AF XY: 0.0000702 AC XY: 51 AN XY: 727008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00124

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74430

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000297 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	5.0
Dann	Benign	0.78
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.17
Sift	Benign	0.55	T
Sift4G	Benign	0.34	T
Polyphen		0.0090	B
Vest4		0.024
MVP		0.58
MPC		0.17
ClinPred		0.015	T
GERP RS		-7.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.038
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs140712582; hg19: chr3-132277849;