rs200094110

Variant names:

• chr11-44077347-C-T
• rs200094110
• NM_032592.4:c.625C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-44077347-C-T
• chr11-44077347-C-A
• chr11-44077347-C-G

Variant summary

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

The NM_032592.4(ACCS):​c.625C>T​(p.Arg209Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000427 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: ACCS NM_032592.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• 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 2 ACMG points.

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

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.625C>T	p.Arg209Trp	missense	Exon 7 of 15	NP_115981.1	A0A0S2Z622
	ACCS	NM_001127219.2		c.625C>T	p.Arg209Trp	missense	Exon 7 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.625C>T	p.Arg209Trp	missense	Exon 7 of 15	ENSP00000263776.8	Q96QU6-1
	ACCS	ENST00000894384.1		c.625C>T	p.Arg209Trp	missense	Exon 7 of 15	ENSP00000564443.1
	ACCS	ENST00000964372.1		c.625C>T	p.Arg209Trp	missense	Exon 7 of 15	ENSP00000634431.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251416 AF XY: 0.0000368

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1461860 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28 AN XY: 727232

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111992

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000135 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.62
MVP		0.61
MPC		0.48
ClinPred		0.74	D
GERP RS		4.9
Varity_R		0.59
gMVP		0.42
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200094110; hg19: chr11-44098897;