15-78173785-T-G

Position:

• chr15-78173785-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015162.5(ACSBG1):​c.1897A>C​(p.Met633Leu) 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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. M633T) 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: -0.827

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030413479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSBG1	NM_015162.5	c.1897A>C	p.Met633Leu	missense_variant	13/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG1	ENST00000258873.9	c.1897A>C	p.Met633Leu	missense_variant	13/14	1	NM_015162.5	P1
ACSBG1	ENST00000560817.5	c.1171A>C	p.Met391Leu	missense_variant	9/10	5
ACSBG1	ENST00000560183.1	n.483A>C		non_coding_transcript_exon_variant	2/2	2
ACSBG1	ENST00000560124.5	c.*1209A>C		3_prime_UTR_variant, NMD_transcript_variant	9/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.1
DANN	Benign	0.66
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.030	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.63	N;N
REVEL	Benign	0.051
Sift	Benign	0.69	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.43		Loss of catalytic residue at M633 (P = 0.0246);.;
MVP		0.12
MPC		0.31
ClinPred		0.13	T
GERP RS		-0.040
Varity_R		0.046
gMVP		0.55

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: rs2304824; hg19: chr15-78466127;