chr19-6165996-T-C

Position:

• chr19-6165996-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030924.5(ACSBG2):​c.719T>C​(p.Val240Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACSBG2 NM_030924.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

Genes affected

ACSBG2 (HGNC:24174): (acyl-CoA synthetase bubblegum family member 2) Enables acyl-CoA hydrolase activity and arachidonate-CoA ligase activity. Acts upstream of or within fatty acid metabolic process. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

RFX2 (HGNC:9983): (regulatory factor X2) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. This protein can bind to cis elements in the promoter of the IL-5 receptor alpha gene. Two transcript variants encoding different isoforms have been described for this gene, and both variants utilize alternative polyadenylation sites. [provided by RefSeq, Jul 2008]

LOC105372255 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSBG2	NM_030924.5	c.719T>C	p.Val240Ala	missense_variant	7/15	ENST00000588485.6	NP_112186.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSBG2	ENST00000588485.6	c.719T>C	p.Val240Ala	missense_variant	7/15	1	NM_030924.5	ENSP00000466336.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.719T>C (p.V240A) alteration is located in exon 7 (coding exon 6) of the ACSBG2 gene. This alteration results from a T to C substitution at nucleotide position 719, causing the valine (V) at amino acid position 240 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.029	.;.;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D;D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	.;.;L;L
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.071	T;T;T;T
Polyphen		0.021	.;.;B;B
Vest4		0.48
MutPred		0.87		.;.;Gain of disorder (P = 0.0551);Gain of disorder (P = 0.0551);
MVP		0.53
MPC		0.057
ClinPred		0.23	T
GERP RS		3.0
Varity_R		0.21
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs756393677; hg19: chr19-6166007;