NM_001394090.1:c.*292G>A

Variant names:

• chr3-128910007-C-T
• rs766039847
• NM_001394090.1:c.*292G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001394090.1(CFAP92):​c.*292G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,758 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CFAP92 NM_001394090.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240
• Publications: 0 publications found

Genes affected

CFAP92 (HGNC:29231): (cilia and flagella associated protein 92 (putative))

ACAD9 (HGNC:21497): (acyl-CoA dehydrogenase family member 9) This gene encodes a member of the acyl-CoA dehydrogenase family. Members of this family of proteins localize to the mitochondria and catalyze the rate-limiting step in the beta-oxidation of fatty acyl-CoA. The encoded protein is specifically active toward palmitoyl-CoA and long-chain unsaturated substrates. Mutations in this gene cause acyl-CoA dehydrogenase family member type 9 deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

ACAD9 Gene-Disease associations (from GenCC):

• acyl-CoA dehydrogenase 9 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-128910007-C-T is Benign according to our data. Variant chr3-128910007-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2199232.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394090.1. 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
	CFAP92	NM_001394090.1	MANE Select	c.*292G>A		3_prime_UTR	Exon 16 of 16	NP_001381019.1	A0A2R8YFM9
	ACAD9	NM_014049.5	MANE Select	c.1564-14C>T		intron	N/A	NP_054768.2
	CFAP92	NM_001348520.2		c.*292G>A		3_prime_UTR	Exon 15 of 15	NP_001335449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP92	ENST00000645291.3	MANE Select	c.*292G>A		3_prime_UTR	Exon 16 of 16	ENSP00000496592.2	A0A2R8YFM9
	ACAD9	ENST00000308982.12	TSL:1 MANE Select	c.1564-14C>T		intron	N/A	ENSP00000312618.7	Q9H845
	ACAD9	ENST00000511526.5	TSL:1	n.1097-14C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247082 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460524 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726380

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111678

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.024

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

Other links and lift over

dbSNP: rs766039847; hg19: chr3-128628850;