3-128909966-A-G

Variant names:

• chr3-128909966-A-G
• rs6797917
• NM_001394090.1:c.*333T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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 VariationId 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.

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.*333T>C		3_prime_UTR	Exon 16 of 16	NP_001381019.1	A0A2R8YFM9
	ACAD9	NM_014049.5	MANE Select	c.1564-55A>G		intron	N/A	NP_054768.2
	CFAP92	NM_001348520.2		c.*333T>C		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.*333T>C		3_prime_UTR	Exon 16 of 16	ENSP00000496592.2	A0A2R8YFM9
	ACAD9	ENST00000308982.12	TSL:1 MANE Select	c.1564-55A>G		intron	N/A	ENSP00000312618.7	Q9H845
	ACAD9	ENST00000511526.5	TSL:1	n.1097-55A>G		intron	N/A

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

African (AFR) AF: 0.125 AC: 4172 AN: 33440

American (AMR) AF: 0.0125 AC: 530 AN: 42460

Ashkenazi Jewish (ASJ) AF: 0.0198 AC: 509 AN: 25764

East Asian (EAS) AF: 0.0502 AC: 1979 AN: 39394

South Asian (SAS) AF: 0.101 AC: 8504 AN: 83858

European-Finnish (FIN) AF: 0.0408 AC: 2154 AN: 52814

Middle Eastern (MID) AF: 0.0122 AC: 70 AN: 5742

European-Non Finnish (NFE) AF: 0.00938 AC: 10387 AN: 1107936

Other (OTH) AF: 0.0288 AC: 1733 AN: 60070

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

African (AFR) AF: 0.117 AC: 4869 AN: 41554

American (AMR) AF: 0.0226 AC: 346 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.0584 AC: 303 AN: 5186

South Asian (SAS) AF: 0.110 AC: 531 AN: 4828

European-Finnish (FIN) AF: 0.0385 AC: 409 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 691 AN: 68030

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0266 Hom.: 47

Bravo AF: 0.0481

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.47
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6797917; hg19: chr3-128628809;