Variant 11-44078714-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032592.4(ACCS):c.763A>G(p.Ser255Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ACCS
NM_032592.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.97

Variant links:

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]

ACCS links:

ACCS (HGNC:):

ACCS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACCS	NM_032592.4 linkuse as main transcript	c.763A>G	p.Ser255Gly	missense_variant	9/15	ENST00000263776.9	NP_115981.1	Q96QU6-1A0A0S2Z622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACCS	ENST00000263776.9 linkuse as main transcript	c.763A>G	p.Ser255Gly	missense_variant	9/15	1	NM_032592.4	ENSP00000263776.8	Q96QU6-1
ACCS	ENST00000527346.5 linkuse as main transcript	n.1454A>G		non_coding_transcript_exon_variant	2/7	2
ACCS	ENST00000531940.1 linkuse as main transcript	n.1087A>G		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251442

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727234

show subpopulations

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:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

The c.763A>G (p.S255G) alteration is located in exon 9 (coding exon 8) of the ACCS gene. This alteration results from a A to G substitution at nucleotide position 763, causing the serine (S) at amino acid position 255 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Benign

0.087

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.080

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

0.042

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.54

Sift

Uncertain

0.010

Sift4G

Uncertain

0.013

Polyphen

0.0040

Vest4

0.52

MutPred

0.92

Loss of stability (P = 0.1066);

MVP

0.86

MPC

0.088

ClinPred

0.69

GERP RS

4.8

Varity_R

0.39

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over