11-26359258-C-A

Position:

• chr11-26359258-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031418.4(ANO3):​c.46+26937C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,144 control chromosomes in the GnomAD database, including 1,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1007 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO3	NM_031418.4	c.46+26937C>A		intron_variant		ENST00000256737.8	NP_113606.2
ANO3	NM_001313726.2	c.229+49539C>A		intron_variant			NP_001300655.1
ANO3	XM_047427399.1	c.46+26937C>A		intron_variant			XP_047283355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8	c.46+26937C>A		intron_variant		1	NM_031418.4	ENSP00000256737	P3
ANO3	ENST00000525139.5	c.-3+49539C>A		intron_variant		5		ENSP00000432576
ANO3	ENST00000531646.1	c.46+26937C>A		intron_variant		4		ENSP00000435275
ANO3	ENST00000672621.1	c.229+49539C>A		intron_variant				ENSP00000500506

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16468 AN: 152026 Hom.: 1008 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16468 AN: 152144 Hom.: 1007 Cov.: 32 AF XY: 0.111 AC XY: 8246 AN XY: 74366

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.0830

Gnomad4 NFE AF: 0.0966

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0990 Hom.: 1110

Bravo AF: 0.103

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs10834971; hg19: chr11-26380805;