chr20-25020034-A-T

Position:

• chr20-25020034-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032501.4(ACSS1):​c.1222T>A​(p.Ser408Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS1	NM_032501.4	c.1222T>A	p.Ser408Thr	missense_variant	7/14	ENST00000323482.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS1	ENST00000323482.9	c.1222T>A	p.Ser408Thr	missense_variant	7/14	1	NM_032501.4	P1
ACSS1	ENST00000432802.6	c.1222T>A	p.Ser408Thr	missense_variant	7/12	2
ACSS1	ENST00000537502.5	c.859T>A	p.Ser287Thr	missense_variant	6/13	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.1222T>A (p.S408T) alteration is located in exon 7 (coding exon 7) of the ACSS1 gene. This alteration results from a T to A substitution at nucleotide position 1222, causing the serine (S) at amino acid position 408 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	.;.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	.;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.031	.;D;D
Sift4G	Benign	0.065	T;T;T
Polyphen		0.94	.;.;P
Vest4		0.57
MutPred		0.71		.;Gain of ubiquitination at K404 (P = 0.0601);Gain of ubiquitination at K404 (P = 0.0601);
MVP		0.71
MPC		1.3
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.57
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-25000670;