Genetic Variant NM_014049.5:c.11G>T (chr3-128879702-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014049.5(ACAD9):c.11G>T(p.Cys4Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. C4C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ACAD9
NM_014049.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

Publications

0 publications found

Variant links:

Genes affected

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 links:

ACAD9-DT (HGNC:56086): (ACAD9 divergent transcript)

ACAD9-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16834664).

BP6

Variant 3-128879702-G-T is Benign according to our data. Variant chr3-128879702-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 213994.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014049.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACAD9	NM_014049.5	MANE Select	c.11G>T	p.Cys4Phe	missense	Exon 1 of 18	NP_054768.2
ACAD9	NM_001410805.1		c.-265G>T		5_prime_UTR	Exon 1 of 17	NP_001397734.1	Q9H9W4
ACAD9	NR_033426.2		n.83G>T		non_coding_transcript_exon	Exon 1 of 18

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACAD9	ENST00000308982.12	TSL:1 MANE Select	c.11G>T	p.Cys4Phe	missense	Exon 1 of 18	ENSP00000312618.7	Q9H845
ACAD9	ENST00000681367.1		c.11G>T	p.Cys4Phe	missense	Exon 1 of 19	ENSP00000505309.1	A0A7P0T8U3
ACAD9	ENST00000680636.1		c.11G>T	p.Cys4Phe	missense	Exon 1 of 18	ENSP00000504886.1	A0A7P0T7Z1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

4.6

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.0044

MutationAssessor

Uncertain

2.6

PhyloP100

-1.1

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.55

REVEL

Benign

0.26

Sift

Uncertain

0.023

Sift4G

Benign

0.11

Polyphen

0.028

Vest4

0.22

MutPred

0.32

Loss of catalytic residue at C4 (P = 0.0537)

MVP

0.80

MPC

0.35

ClinPred

0.056

GERP RS

-0.18

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.11

gMVP

0.51

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over