rs373838309

Variant names:

• chr20-25007785-C-A
• rs373838309
• NM_032501.4:c.2047G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-25007785-C-A
• chr20-25007785-C-T

Variant summary

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

The NM_032501.4(ACSS1):​c.2047G>T​(p.Asp683Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D683N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACSS1 NM_032501.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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: 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=0.21605179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS1	NM_032501.4	c.2047G>T	p.Asp683Tyr	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.2047G>T	p.Asp683Tyr	missense_variant	Exon 14 of 14	1	NM_032501.4	ENSP00000316924.4
ACSS1	ENST00000484396.1	n.3214G>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
ACSS1	ENST00000537502.5	c.1684G>T	p.Asp562Tyr	missense_variant	Exon 13 of 13	2		ENSP00000439304.2
ACSS1	ENST00000432802.6	c.1663-860G>T		intron_variant	Intron 11 of 11	2		ENSP00000388793.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;T
Eigen	Benign	0.034
Eigen_PC	Benign	0.0017
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	2.0	.;M
PhyloP100		1.3
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	.;N
REVEL	Benign	0.077
Sift	Uncertain	0.0050	.;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.96	.;D
Vest4		0.26
MutPred		0.37		.;Gain of helix (P = 0.0117);
MVP		0.53
MPC		0.99
ClinPred		0.55	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.54
Mutation Taster		=88/12	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: rs373838309; hg19: chr20-24988421; COSMIC: COSV100053539;