19-6151764-T-C

Position:

• chr19-6151764-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000588485.6(ACSBG2):​c.355T>C​(p.Phe119Leu) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACSBG2 ENST00000588485.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13045087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSBG2	NM_030924.5	c.355T>C	p.Phe119Leu	missense_variant	4/15	ENST00000588485.6	NP_112186.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSBG2	ENST00000588485.6	c.355T>C	p.Phe119Leu	missense_variant	4/15	1	NM_030924.5	ENSP00000466336.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Jan 03, 2024

The c.355T>C (p.F119L) alteration is located in exon 4 (coding exon 3) of the ACSBG2 gene. This alteration results from a T to C substitution at nucleotide position 355, causing the phenylalanine (F) at amino acid position 119 to be replaced by a leucine (L). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.5
DANN	Benign	0.89
DEOGEN2	Benign	0.071	T;.;T;T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.84	T;T;T;.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	.;.;.;N;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.62	T;T;T;T;T
Polyphen		0.041	.;.;.;B;B
Vest4		0.42, 0.42
MutPred		0.67		Loss of catalytic residue at F119 (P = 0.053);.;Loss of catalytic residue at F119 (P = 0.053);Loss of catalytic residue at F119 (P = 0.053);Loss of catalytic residue at F119 (P = 0.053);
MVP		0.15
MPC		0.052
ClinPred		0.052	T
GERP RS		-2.0
Varity_R		0.13
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6151775;