11-26332444-TAAA-TA

Variant names:

• chr11-26332444-TAA-T
• rs56225203
• NM_031418.4:c.46+138_46+139delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_031418.4(ANO3):​c.46+138_46+139delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 611,016 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0089 (0 hom.)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000759 (102/134336) while in subpopulation AFR AF= 0.00256 (92/35998). AF 95% confidence interval is 0.00213. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4	c.46+138_46+139delAA		intron_variant	Intron 1 of 26	ENST00000256737.8	NP_113606.2
ANO3	NM_001313726.2	c.229+22740_229+22741delAA		intron_variant	Intron 2 of 27		NP_001300655.1
ANO3	XM_047427399.1	c.46+138_46+139delAA		intron_variant	Intron 1 of 25		XP_047283355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8	c.46+124_46+125delAA		intron_variant	Intron 1 of 26	1	NM_031418.4	ENSP00000256737.3
ANO3	ENST00000672621.1	c.229+22726_229+22727delAA		intron_variant	Intron 2 of 27			ENSP00000500506.1
ANO3	ENST00000525139.5	c.-3+22726_-3+22727delAA		intron_variant	Intron 1 of 26	5		ENSP00000432576.1
ANO3	ENST00000531646.1	c.46+124_46+125delAA		intron_variant	Intron 1 of 4	4		ENSP00000435275.1

Frequencies

GnomAD3 genomes AF: 0.000752 AC: 101 AN: 134302 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000720

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000312

Gnomad OTH AF: 0.000561

GnomAD4 exome AF: 0.00890 AC: 4241 AN: 476680 Hom.: 0 AF XY: 0.00884 AC XY: 2217 AN XY: 250690

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.00830

Gnomad4 ASJ exome AF: 0.00906

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.00929

Gnomad4 FIN exome AF: 0.00493

Gnomad4 NFE exome AF: 0.00742

Gnomad4 OTH exome AF: 0.00902

GnomAD4 genome AF: 0.000759 AC: 102 AN: 134336 Hom.: 0 Cov.: 0 AF XY: 0.000710 AC XY: 45 AN XY: 63392

Gnomad4 AFR AF: 0.00256

Gnomad4 AMR AF: 0.000160

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000720

Gnomad4 NFE AF: 0.0000312

Gnomad4 OTH AF: 0.000557

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs56225203; hg19: chr11-26353991;