rs1239930426

Variant names:

• chr11-44067887-A-G
• rs1239930426
• NM_032592.4:c.260A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-44067887-A-G
• chr11-44067887-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032592.4(ACCS):​c.260A>G​(p.Asp87Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D87V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACCS NM_032592.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCS	NM_032592.4	MANE Select	c.260A>G	p.Asp87Gly	missense	Exon 2 of 15	NP_115981.1	A0A0S2Z622
	ACCS	NM_001127219.2		c.260A>G	p.Asp87Gly	missense	Exon 2 of 15	NP_001120691.1	A0A0S2Z622

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCS	ENST00000263776.9	TSL:1 MANE Select	c.260A>G	p.Asp87Gly	missense	Exon 2 of 15	ENSP00000263776.8	Q96QU6-1
	ACCS	ENST00000527603.5	TSL:1	n.325+113A>G		intron	N/A
	ACCS	ENST00000894384.1		c.260A>G	p.Asp87Gly	missense	Exon 2 of 15	ENSP00000564443.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246270 AF XY: 0.00000752

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457598 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 724938

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000300 AC: 1 AN: 33320

American (AMR) AF: 0.00 AC: 0 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25586

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 85568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109982

Other (OTH) AF: 0.00 AC: 0 AN: 60210

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	35
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.61	T
PhyloP100		6.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.54		Loss of helix (P = 0.0626)
MVP		0.75
MPC		0.43
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.57
gMVP		0.52
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_DG_spliceai		1.0		Position offset: -1
DS_DL_spliceai		0.99		Position offset: 28

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1239930426; hg19: chr11-44089437;