NM_032501.4:c.1967C>T

Variant names:

• chr20-25007865-G-A
• NM_032501.4:c.1967C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032501.4(ACSS1):​c.1967C>T​(p.Ala656Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACSS1 NM_032501.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

Genes affected

ACSS1 (HGNC:16091): (acyl-CoA synthetase short chain family member 1) This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

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=0.03230977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS1	NM_032501.4	c.1967C>T	p.Ala656Val	missense_variant	Exon 14 of 14	ENST00000323482.9	NP_115890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS1	ENST00000323482.9	c.1967C>T	p.Ala656Val	missense_variant	Exon 14 of 14	1	NM_032501.4	ENSP00000316924.4
ACSS1	ENST00000484396.1	n.3134C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
ACSS1	ENST00000537502.5	c.1604C>T	p.Ala535Val	missense_variant	Exon 13 of 13	2		ENSP00000439304.2
ACSS1	ENST00000432802.6	c.1663-940C>T		intron_variant	Intron 11 of 11	2		ENSP00000388793.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1967C>T (p.A656V) alteration is located in exon 14 (coding exon 14) of the ACSS1 gene. This alteration results from a C to T substitution at nucleotide position 1967, causing the alanine (A) at amino acid position 656 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.48
DANN	Benign	0.48
DEOGEN2	Benign	0.081	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.090	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.0	.;N
REVEL	Benign	0.012
Sift	Benign	0.57	.;T
Sift4G	Benign	0.60	T;T
Polyphen		0.0	.;B
Vest4		0.033
MutPred		0.30		.;Loss of disorder (P = 0.1041);
MVP		0.23
MPC		0.57
ClinPred		0.020	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.014
gMVP		0.19
Mutation Taster		=95/5	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

hg19: chr20-24988501;