3-128909880-A-G

Position:

• chr3-128909880-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.*419T>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 0.0227 in 1,219,148 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (47 hom., cov: 33)
  • Exomes 𝑓: 0.023 (360 hom.)
• Consequence: CFAP92 NM_001394090.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.766

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=-0.9).
• BP6: Variant 3-128909880-A-G is Benign according to our data. Variant chr3-128909880-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP92	NM_001394090.1	c.*419T>C		3_prime_UTR_variant	16/16	ENST00000645291.3	NP_001381019.1
ACAD9	NM_014049.5	c.1564-141A>G		intron_variant		ENST00000308982.12	NP_054768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP92	ENST00000645291.3	c.*419T>C		3_prime_UTR_variant	16/16		NM_001394090.1	ENSP00000496592	P2
ACAD9	ENST00000308982.12	c.1564-141A>G		intron_variant		1	NM_014049.5	ENSP00000312618	P1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2954 AN: 152134 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0349

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0253

GnomAD4 exome AF: 0.0231 AC: 24692 AN: 1066896 Hom.: 360 Cov.: 14 AF XY: 0.0239 AC XY: 12856 AN XY: 538136

Gnomad4 AFR exome AF: 0.00424

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.0303

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0337

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0194 AC: 2951 AN: 152252 Hom.: 47 Cov.: 33 AF XY: 0.0196 AC XY: 1460 AN XY: 74452

Gnomad4 AFR AF: 0.00474

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0347

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0246 Hom.: 5

Bravo AF: 0.0187

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.45

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: rs75330990; hg19: chr3-128628723;