15-78173605-C-G

Variant names:

• chr15-78173605-C-G
• rs757257520
• NM_015162.5:c.2077G>C

Variant summary

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

The NM_015162.5(ACSBG1):​c.2077G>C​(p.Gly693Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G693S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSBG1 NM_015162.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

Genes affected

ACSBG1 (HGNC:29567): (acyl-CoA synthetase bubblegum family member 1) The protein encoded by this gene possesses long-chain acyl-CoA synthetase activity. It is thought to play a central role in brain very long-chain fatty acids metabolism and myelinogenesis. [provided by RefSeq, Jul 2008]

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, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSBG1	NM_015162.5	c.2077G>C	p.Gly693Arg	missense_variant	Exon 13 of 14	ENST00000258873.9	NP_055977.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSBG1	ENST00000258873.9	c.2077G>C	p.Gly693Arg	missense_variant	Exon 13 of 14	1	NM_015162.5	ENSP00000258873.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0087	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-7.5	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.94	P;.
Vest4		0.70
MutPred		0.55		Gain of solvent accessibility (P = 0.0171);.;
MVP		0.59
MPC		1.2
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.61
gMVP		0.70

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: rs757257520; hg19: chr15-78465947;