chr20-34882891-C-A

Variant names:

• chr20-34882891-C-A
• rs4911163
• NM_018677.4:c.276C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018677.4(ACSS2):​c.276C>A​(p.Phe92Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSS2 NM_018677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707
• Publications: 42 publications found

Genes affected

ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS2	NM_018677.4	MANE Select	c.276C>A	p.Phe92Leu	missense	Exon 2 of 18	NP_061147.1	Q9NR19-1
	ACSS2	NM_001076552.3		c.276C>A	p.Phe92Leu	missense	Exon 2 of 19	NP_001070020.2	Q9NR19-2
	ACSS2	NM_001242393.2		c.-10C>A		5_prime_UTR	Exon 2 of 18	NP_001229322.1	Q4G0E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS2	ENST00000360596.7	TSL:1 MANE Select	c.276C>A	p.Phe92Leu	missense	Exon 2 of 18	ENSP00000353804.2	Q9NR19-1
	ACSS2	ENST00000484354.1	TSL:5	c.252C>A	p.Phe84Leu	missense	Exon 2 of 3	ENSP00000419167.1	C9JXD9
	ACSS2	ENST00000871370.1		c.276C>A	p.Phe92Leu	missense	Exon 2 of 20	ENSP00000541429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.71
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.17
Sift	Benign	0.43	T
Sift4G	Benign	0.30	T
Polyphen		0.76	P
Vest4		0.54
MutPred		0.40		Loss of methylation at K90 (P = 0.0865)
MVP		0.30
MPC		0.33
ClinPred		0.95	D
GERP RS		4.1
Varity_R		0.29
gMVP		0.59
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4911163; hg19: chr20-33470694;