rs150506041

Variant names:

• chr11-26660315-A-G
• rs150506041
• NM_031418.4:c.2817A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-26660315-A-G
• chr11-26660315-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_031418.4(ANO3):​c.2817A>G​(p.Pro939Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,613,518 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (8 hom.)
• Consequence: ANO3 NM_031418.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.622
• Publications: 1 publications found

Genes affected

ANO3 (HGNC:14004): (anoctamin 3) The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ANO3 Gene-Disease associations (from GenCC):

• dystonia 24

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-26660315-A-G is Benign according to our data. Variant chr11-26660315-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.622 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00135 (206/152298) while in subpopulation NFE AF = 0.00203 (138/68014). AF 95% confidence interval is 0.00175. There are 0 homozygotes in GnomAd4. There are 86 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 206 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031418.4. 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
	ANO3	NM_031418.4	MANE Select	c.2817A>G	p.Pro939Pro	synonymous	Exon 27 of 27	NP_113606.2	Q9BYT9-1
	ANO3	NM_001313726.2		c.3000A>G	p.Pro1000Pro	synonymous	Exon 28 of 28	NP_001300655.1	A0A5F9ZHL6
	ANO3	NM_001313727.2		c.2379A>G	p.Pro793Pro	synonymous	Exon 24 of 24	NP_001300656.1	Q9BYT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.2817A>G	p.Pro939Pro	synonymous	Exon 27 of 27	ENSP00000256737.3	Q9BYT9-1
	ANO3	ENST00000672621.1		c.3000A>G	p.Pro1000Pro	synonymous	Exon 28 of 28	ENSP00000500506.1	A0A5F9ZHL6
	ANO3	ENST00000525139.5	TSL:5	c.2769A>G	p.Pro923Pro	synonymous	Exon 27 of 27	ENSP00000432576.1	E9PQ79

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 207 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00155 AC: 388 AN: 250892 AF XY: 0.00147

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000728

Gnomad ASJ exome AF: 0.00427

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.00212

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00192 AC: 2805 AN: 1461220 Hom.: 8 Cov.: 31 AF XY: 0.00190 AC XY: 1381 AN XY: 726918

African (AFR) AF: 0.000329 AC: 11 AN: 33426

American (AMR) AF: 0.000806 AC: 36 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 113 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86146

European-Finnish (FIN) AF: 0.00208 AC: 111 AN: 53414

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5760

European-Non Finnish (NFE) AF: 0.00212 AC: 2354 AN: 1111636

Other (OTH) AF: 0.00179 AC: 108 AN: 60370

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00116 AC XY: 86 AN XY: 74456

African (AFR) AF: 0.000505 AC: 21 AN: 41588

American (AMR) AF: 0.000851 AC: 13 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00203 AC: 138 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00129

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00303

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ANO3-related disorder (1)
-	-	1	Dystonia 24 (1)
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.6
DANN	Benign	0.74
PhyloP100		0.62
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs150506041; hg19: chr11-26681862; COSMIC: COSV56783933;