11-44083177-A-G

Position:

• chr11-44083177-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000263776.9(ACCS):​c.1120A>G​(p.Asn374Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N374S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACCS ENST00000263776.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

Genes affected

ACCS (HGNC:23989): (1-aminocyclopropane-1-carboxylate synthase homolog (inactive)) Enables identical protein binding activity. Predicted to be involved in biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15692523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACCS	NM_032592.4	c.1120A>G	p.Asn374Asp	missense_variant	13/15	ENST00000263776.9	NP_115981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACCS	ENST00000263776.9	c.1120A>G	p.Asn374Asp	missense_variant	13/15	1	NM_032592.4	ENSP00000263776	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

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

Feb 16, 2023

The c.1120A>G (p.N374D) alteration is located in exon 13 (coding exon 12) of the ACCS gene. This alteration results from a A to G substitution at nucleotide position 1120, causing the asparagine (N) at amino acid position 374 to be replaced by an aspartic acid (D). 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	0.069
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.60
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	-0.17	N
MutationTaster	Benign	0.97	D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.33	N
REVEL	Uncertain	0.31
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.37
MutPred		0.36		Gain of phosphorylation at Y377 (P = 0.0922);
MVP		0.76
MPC		0.11
ClinPred		0.50	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.43

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: chr11-44104727;