rs1388854975

Variant names:

• chr20-34876675-C-A
• rs1388854975
• NM_018677.4:c.30C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-34876675-C-A
• chr20-34876675-C-G
• chr20-34876675-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018677.4(ACSS2):​c.30C>A​(p.Ser10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000795 in 1,257,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: ACSS2 NM_018677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113227785).

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.30C>A	p.Ser10Arg	missense	Exon 1 of 18	NP_061147.1	Q9NR19-1
	ACSS2	NM_001076552.3		c.30C>A	p.Ser10Arg	missense	Exon 1 of 19	NP_001070020.2	Q9NR19-2
	ACSS2	NM_001242393.2		c.-108+1538C>A		intron	N/A	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.30C>A	p.Ser10Arg	missense	Exon 1 of 18	ENSP00000353804.2	Q9NR19-1
	ACSS2	ENST00000484354.1	TSL:5	c.30C>A	p.Ser10Arg	missense	Exon 1 of 3	ENSP00000419167.1	C9JXD9
	ACSS2	ENST00000871370.1		c.30C>A	p.Ser10Arg	missense	Exon 1 of 20	ENSP00000541429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.95e-7 AC: 1 AN: 1257448 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 613802

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25122

American (AMR) AF: 0.00 AC: 0 AN: 17572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19504

East Asian (EAS) AF: 0.00 AC: 0 AN: 28350

South Asian (SAS) AF: 0.00 AC: 0 AN: 60226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3652

European-Non Finnish (NFE) AF: 9.93e-7 AC: 1 AN: 1006664

Other (OTH) AF: 0.00 AC: 0 AN: 50724

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.62
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.047	B
Vest4		0.22
MutPred		0.21		Loss of phosphorylation at S10 (P = 9e-04)
MVP		0.41
MPC		1.6
ClinPred		0.10	T
GERP RS		1.8
PromoterAI		0.0098	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1
Varity_R		0.15
gMVP		0.54
Mutation Taster		=98/2	polymorphism

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: rs1388854975; hg19: chr20-33464478;