NM_032592.4:c.606G>A

Variant names:

• chr11-44077328-G-A
• rs79793705
• NM_032592.4:c.606G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032592.4(ACCS):​c.606G>A​(p.Val202Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,614,168 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (9 hom.)
• Consequence: ACCS NM_032592.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.382
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-44077328-G-A is Benign according to our data. Variant chr11-44077328-G-A is described in ClinVar as Benign. ClinVar VariationId is 709994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.382 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0052 (792/152302) while in subpopulation AFR AF = 0.018 (748/41574). AF 95% confidence interval is 0.0169. There are 10 homozygotes in GnomAd4. There are 381 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.606G>A	p.Val202Val	synonymous	Exon 7 of 15	NP_115981.1	A0A0S2Z622
	ACCS	NM_001127219.2		c.606G>A	p.Val202Val	synonymous	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.606G>A	p.Val202Val	synonymous	Exon 7 of 15	ENSP00000263776.8	Q96QU6-1
	ACCS	ENST00000894384.1		c.606G>A	p.Val202Val	synonymous	Exon 7 of 15	ENSP00000564443.1
	ACCS	ENST00000964372.1		c.606G>A	p.Val202Val	synonymous	Exon 7 of 15	ENSP00000634431.1

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 793 AN: 152184 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00135 AC: 339 AN: 251426 AF XY: 0.000913

Gnomad AFR exome AF: 0.0184

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000473 AC: 692 AN: 1461866 Hom.: 9 Cov.: 30 AF XY: 0.000392 AC XY: 285 AN XY: 727236

African (AFR) AF: 0.0171 AC: 573 AN: 33480

American (AMR) AF: 0.000894 AC: 40 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

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

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111994

Other (OTH) AF: 0.000861 AC: 52 AN: 60392

GnomAD4 genome AF: 0.00520 AC: 792 AN: 152302 Hom.: 10 Cov.: 32 AF XY: 0.00512 AC XY: 381 AN XY: 74462

African (AFR) AF: 0.0180 AC: 748 AN: 41574

American (AMR) AF: 0.00203 AC: 31 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00209 Hom.: 1

Bravo AF: 0.00600

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.38
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79793705; hg19: chr11-44098878;