3-128909970-G-A

Variant names:

• chr3-128909970-G-A
• rs115174494
• NM_001394090.1:c.*329C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001394090.1(CFAP92):​c.*329C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,605,254 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (14 hom., cov: 33)
  • Exomes 𝑓: 0.016 (195 hom.)
• Consequence: CFAP92 NM_001394090.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.348
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-128909970-G-A is Benign according to our data. Variant chr3-128909970-G-A is described in ClinVar as Benign. ClinVar VariationId is 2654113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0113 (1717/152360) while in subpopulation NFE AF = 0.0174 (1185/68032). AF 95% confidence interval is 0.0166. There are 14 homozygotes in GnomAd4. There are 801 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 gene

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.*329C>T		3_prime_UTR	Exon 16 of 16	NP_001381019.1	A0A2R8YFM9
	ACAD9	NM_014049.5	MANE Select	c.1564-51G>A		intron	N/A	NP_054768.2
	CFAP92	NM_001348520.2		c.*329C>T		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.*329C>T		3_prime_UTR	Exon 16 of 16	ENSP00000496592.2	A0A2R8YFM9
	ACAD9	ENST00000308982.12	TSL:1 MANE Select	c.1564-51G>A		intron	N/A	ENSP00000312618.7	Q9H845
	ACAD9	ENST00000511526.5	TSL:1	n.1097-51G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1717 AN: 152242 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.0122 AC: 2885 AN: 235516 AF XY: 0.0128

Gnomad AFR exome AF: 0.00255

Gnomad AMR exome AF: 0.00546

Gnomad ASJ exome AF: 0.00406

Gnomad EAS exome AF: 0.0000578

Gnomad FIN exome AF: 0.0182

Gnomad NFE exome AF: 0.0177

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0160 AC: 23220 AN: 1452894 Hom.: 195 Cov.: 32 AF XY: 0.0158 AC XY: 11379 AN XY: 721716

African (AFR) AF: 0.00251 AC: 84 AN: 33438

American (AMR) AF: 0.00555 AC: 238 AN: 42886

Ashkenazi Jewish (ASJ) AF: 0.00504 AC: 130 AN: 25776

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39460

South Asian (SAS) AF: 0.0106 AC: 894 AN: 84168

European-Finnish (FIN) AF: 0.0185 AC: 979 AN: 52918

Middle Eastern (MID) AF: 0.00314 AC: 18 AN: 5740

European-Non Finnish (NFE) AF: 0.0180 AC: 19959 AN: 1108412

Other (OTH) AF: 0.0152 AC: 916 AN: 60096

GnomAD4 genome AF: 0.0113 AC: 1717 AN: 152360 Hom.: 14 Cov.: 33 AF XY: 0.0108 AC XY: 801 AN XY: 74502

African (AFR) AF: 0.00310 AC: 129 AN: 41580

American (AMR) AF: 0.00804 AC: 123 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

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

South Asian (SAS) AF: 0.00786 AC: 38 AN: 4832

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1185 AN: 68032

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00787 Hom.: 3

Bravo AF: 0.00965

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.92
CADD	Benign	0.20
DANN	Benign	0.26
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs115174494; hg19: chr3-128628813;