3-128909966-A-G

Position:

• chr3-128909966-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394090.1(CFAP92):​c.*333T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,603,790 control chromosomes in the GnomAD database, including 1,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (355 hom., cov: 33)
  • Exomes 𝑓: 0.021 (1026 hom.)
• Consequence: CFAP92 NM_001394090.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.246

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 3-128909966-A-G is Benign according to our data. Variant chr3-128909966-A-G is described in ClinVar as [Benign]. Clinvar id is 676562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP92	NM_001394090.1	c.*333T>C		3_prime_UTR_variant	16/16	ENST00000645291.3
ACAD9	NM_014049.5	c.1564-55A>G		intron_variant		ENST00000308982.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP92	ENST00000645291.3	c.*333T>C		3_prime_UTR_variant	16/16		NM_001394090.1	P2
ACAD9	ENST00000308982.12	c.1564-55A>G		intron_variant		1	NM_014049.5	P1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7256 AN: 152194 Hom.: 353 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0310

GnomAD4 exome AF: 0.0207 AC: 30038 AN: 1451478 Hom.: 1026 Cov.: 32 AF XY: 0.0225 AC XY: 16255 AN XY: 720924

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0198

Gnomad4 EAS exome AF: 0.0502

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0408

Gnomad4 NFE exome AF: 0.00938

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0477 AC: 7268 AN: 152312 Hom.: 355 Cov.: 33 AF XY: 0.0495 AC XY: 3687 AN XY: 74474

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0252 Hom.: 31

Bravo AF: 0.0481

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6797917; hg19: chr3-128628809;