11-26660315-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_031418.4(ANO3):​c.2817A>T​(p.Pro939Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P939P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANO3 NM_031418.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.622 with no splicing effect.

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>T	p.Pro939Pro	synonymous	Exon 27 of 27	NP_113606.2	Q9BYT9-1
	ANO3	NM_001313726.2		c.3000A>T	p.Pro1000Pro	synonymous	Exon 28 of 28	NP_001300655.1	A0A5F9ZHL6
	ANO3	NM_001313727.2		c.2379A>T	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>T	p.Pro939Pro	synonymous	Exon 27 of 27	ENSP00000256737.3	Q9BYT9-1
	ANO3	ENST00000672621.1		c.3000A>T	p.Pro1000Pro	synonymous	Exon 28 of 28	ENSP00000500506.1	A0A5F9ZHL6
	ANO3	ENST00000525139.5	TSL:5	c.2769A>T	p.Pro923Pro	synonymous	Exon 27 of 27	ENSP00000432576.1	E9PQ79

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.1
DANN	Benign	0.74
PhyloP100		0.62

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

Other links and lift over

dbSNP: rs150506041; hg19: chr11-26681862;