3-132618633-C-T

Variant names:

• chr3-132618633-C-T
• rs41272317
• NM_032169.5:c.1414+1G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032169.5(ACAD11):​c.1414+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,579,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ACAD11 NM_032169.5 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77
• Publications: 14 publications found

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:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACKR4 (HGNC:1611): (atypical chemokine receptor 4) The protein encoded by this gene is a member of the G protein-coupled receptor family, and is a receptor for C-C type chemokines. This receptor has been shown to bind dendritic cell- and T cell-activated chemokines including CCL19/ELC, CCL21/SLC, and CCL25/TECK. A pseudogene of this gene is found on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032169.5. 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
	ACAD11	NM_032169.5	MANE Select	c.1414+1G>A		splice_donor intron	N/A	NP_115545.3
	NPHP3-ACAD11	NR_037804.1		n.5416+1G>A		splice_donor intron	N/A
	ACAD11	NR_132426.2		n.1472+1G>A		splice_donor intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD11	ENST00000264990.11	TSL:1 MANE Select	c.1414+1G>A		splice_donor intron	N/A	ENSP00000264990.6
	ACAD11	ENST00000485198.5	TSL:1	n.1197+8058G>A		intron	N/A	ENSP00000419973.1
	ACAD11	ENST00000481970.2	TSL:5	c.1415G>A	p.Gly472Asp	missense	Exon 11 of 11	ENSP00000420907.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000401 AC: 9 AN: 224206 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000214

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000665

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000189 AC: 27 AN: 1427754 Hom.: 0 Cov.: 30 AF XY: 0.0000211 AC XY: 15 AN XY: 710076

African (AFR) AF: 0.00 AC: 0 AN: 31276

American (AMR) AF: 0.00 AC: 0 AN: 38212

Ashkenazi Jewish (ASJ) AF: 0.000159 AC: 4 AN: 25224

East Asian (EAS) AF: 0.00 AC: 0 AN: 37242

South Asian (SAS) AF: 0.00 AC: 0 AN: 80144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52786

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5652

European-Non Finnish (NFE) AF: 0.0000173 AC: 19 AN: 1098284

Other (OTH) AF: 0.0000509 AC: 3 AN: 58934

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68018

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00000832 Hom.: 117

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Uncertain	0.12	D
PhyloP100		7.8
ClinPred		0.45	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/100	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		0.91		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.91		Position offset: 1

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

Other links and lift over

dbSNP: rs41272317; hg19: chr3-132337477;