rs143890712

Variant names:

• chr20-25007818-C-A
• rs143890712
• NM_032501.4:c.2014G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-25007818-C-A
• chr20-25007818-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032501.4(ACSS1):​c.2014G>T​(p.Ala672Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ACSS1 NM_032501.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060237825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS1	NM_032501.4	c.2014G>T	p.Ala672Ser	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.2014G>T	p.Ala672Ser	missense_variant	Exon 14 of 14	1	NM_032501.4	ENSP00000316924.4
ACSS1	ENST00000484396.1	n.3181G>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
ACSS1	ENST00000537502.5	c.1651G>T	p.Ala551Ser	missense_variant	Exon 13 of 13	2		ENSP00000439304.2
ACSS1	ENST00000432802.6	c.1663-893G>T		intron_variant	Intron 11 of 11	2		ENSP00000388793.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.025
DANN	Benign	0.51
DEOGEN2	Benign	0.088	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	.;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.0	.;N
REVEL	Benign	0.046
Sift	Benign	0.099	.;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0	.;B
Vest4		0.060
MutPred		0.36		.;Gain of disorder (P = 0.0274);
MVP		0.26
MPC		0.52
ClinPred		0.033	T
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.080

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

Publications

LitVar

Other links and lift over

dbSNP: rs143890712; hg19: chr20-24988454;