chr15-78173785-T-G

Variant names:

• chr15-78173785-T-G
• rs2304824
• NM_015162.5:c.1897A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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 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
• Publications: 32 publications found

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

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=0.030413479).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015162.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSBG1	NM_015162.5	MANE Select	c.1897A>C	p.Met633Leu	missense	Exon 13 of 14	NP_055977.3
	ACSBG1	NM_001199377.2		c.1885A>C	p.Met629Leu	missense	Exon 13 of 14	NP_001186306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSBG1	ENST00000258873.9	TSL:1 MANE Select	c.1897A>C	p.Met633Leu	missense	Exon 13 of 14	ENSP00000258873.4
	ACSBG1	ENST00000560817.5	TSL:5	c.1171A>C	p.Met391Leu	missense	Exon 9 of 10	ENSP00000453451.1
	ACSBG1	ENST00000560124.5	TSL:2	n.*1209A>C		non_coding_transcript_exon	Exon 9 of 10	ENSP00000453605.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.83
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.051
Sift	Benign	0.69	T
Sift4G	Benign	0.59	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

Other links and lift over

dbSNP: rs2304824; hg19: chr15-78466127;