20-34913132-A-C

Variant names:

• chr20-34913132-A-C
• NM_018677.4:c.411A>C
• ACSS2 p.Thr137Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018677.4(ACSS2):​c.411A>C​(p.Thr137Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T137T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSS2 NM_018677.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.

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.411A>C	p.Thr137Thr	synonymous	Exon 3 of 18	NP_061147.1	Q9NR19-1
	ACSS2	NM_001076552.3		c.411A>C	p.Thr137Thr	synonymous	Exon 3 of 19	NP_001070020.2	Q9NR19-2
	ACSS2	NM_001242393.2		c.126A>C	p.Thr42Thr	synonymous	Exon 3 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.411A>C	p.Thr137Thr	synonymous	Exon 3 of 18	ENSP00000353804.2	Q9NR19-1
	ACSS2	ENST00000484354.1	TSL:5	c.387A>C	p.Thr129Thr	synonymous	Exon 3 of 3	ENSP00000419167.1	C9JXD9
	ACSS2	ENST00000871370.1		c.411A>C	p.Thr137Thr	synonymous	Exon 3 of 20	ENSP00000541429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		-0.041

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-33500935;