NM_001609.4:c.39G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001609.4(ACADSB):c.39G>T(p.Arg13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,546,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13K) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACADSB
NM_001609.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

1 publications found

Variant links:

Genes affected

ACADSB (HGNC:91): (acyl-CoA dehydrogenase short/branched chain) Short/branched chain acyl-CoA dehydrogenase(ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. Substrate specificity is the primary characteristic used to define members of this gene family. The ACADSB gene product has the greatest activity towards the short branched chain acyl-CoA derivative, (S)-2-methylbutyryl-CoA, but also reacts significantly with other 2-methyl branched chain substrates and with short straight chain acyl-CoAs. The cDNA encodes for a mitochondrial precursor protein which is cleaved upon mitochondrial import and predicted to yield a mature peptide of approximately 43.7-KDa. [provided by RefSeq, Jul 2008]

ACADSB links:

IKZF5 (HGNC:14283): (IKAROS family zinc finger 5) Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Pegasus, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]

IKZF5 Gene-Disease associations (from GenCC):

thrombocytopenia 7
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
autosomal thrombocytopenia with normal platelets
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IKZF5 links:

Genome browser will be placed here

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=0.06160289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001609.4. 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
	ACADSB	NM_001609.4	MANE Select	c.39G>T	p.Arg13Ser	missense	Exon 1 of 11	NP_001600.1	P45954-1
	ACADSB	NM_001330174.3		c.-167G>T		5_prime_UTR	Exon 1 of 10	NP_001317103.1	P45954-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACADSB	ENST00000358776.7	TSL:1 MANE Select	c.39G>T	p.Arg13Ser	missense	Exon 1 of 11	ENSP00000357873.3	P45954-1
ACADSB	ENST00000908753.1		c.39G>T	p.Arg13Ser	missense	Exon 1 of 10	ENSP00000578812.1
ACADSB	ENST00000908750.1		c.39G>T	p.Arg13Ser	missense	Exon 1 of 10	ENSP00000578809.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394058

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687856

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31584

American (AMR)

AF:

0.00

AC:

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

35726

South Asian (SAS)

AF:

0.00

AC:

AN:

79204

European-Finnish (FIN)

AF:

0.0000225

AC:

AN:

44508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078710

Other (OTH)

AF:

0.00

AC:

AN:

57942

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.093

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.062

MetaSVM

Uncertain

0.013

MutationAssessor

Benign

0.69

PhyloP100

0.094

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.19

REVEL

Uncertain

0.35

Sift

Benign

0.30

Sift4G

Benign

0.088

Polyphen

0.0050

Vest4

0.13

MutPred

0.49

Gain of helix (P = 0.0078)

MVP

0.61

MPC

0.063

ClinPred

0.17

GERP RS

-0.47

PromoterAI

0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.41

Mutation Taster

=63/37

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over