rs4911163

Positions:

• chr20-34882891-C-A
• chr20-34882891-C-G
• chr20-34882891-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACSS2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSS2	NM_018677.4	c.276C>A	p.Phe92Leu	missense_variant	2/18	ENST00000360596.7	NP_061147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS2	ENST00000360596.7	c.276C>A	p.Phe92Leu	missense_variant	2/18	1	NM_018677.4	ENSP00000353804.2
ACSS2	ENST00000484354.1	c.252C>A	p.Phe84Leu	missense_variant	2/3	5		ENSP00000419167.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;T;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.2	.;L;.;.;.;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.43	T;T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.76	.;P;.;.;.;.
Vest4		0.54, 0.54
MutPred		0.40		.;Loss of methylation at K90 (P = 0.0865);.;Loss of methylation at K90 (P = 0.0865);Loss of methylation at K90 (P = 0.0865);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4911163; hg19: chr20-33470694;