11-26332444-TAAA-TAAAAAAAAAA

Variant names:

• chr11-26332444-T-TAAAAAAA
• rs56225203
• NM_031418.4:c.46+133_46+139dupAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_031418.4(ANO3):​c.46+133_46+139dupAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 616,042 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 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_031418.4	c.46+133_46+139dupAAAAAAA		intron_variant	Intron 1 of 26	ENST00000256737.8	NP_113606.2
ANO3	NM_001313726.2	c.229+22735_229+22741dupAAAAAAA		intron_variant	Intron 2 of 27		NP_001300655.1
ANO3	XM_047427399.1	c.46+133_46+139dupAAAAAAA		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+123_46+124insAAAAAAA		intron_variant	Intron 1 of 26	1	NM_031418.4	ENSP00000256737.3
ANO3	ENST00000672621.1	c.229+22725_229+22726insAAAAAAA		intron_variant	Intron 2 of 27			ENSP00000500506.1
ANO3	ENST00000525139.5	c.-3+22725_-3+22726insAAAAAAA		intron_variant	Intron 1 of 26	5		ENSP00000432576.1
ANO3	ENST00000531646.1	c.46+123_46+124insAAAAAAA		intron_variant	Intron 1 of 4	4		ENSP00000435275.1

Frequencies

GnomAD3 genomes AF: 0.0000149 AC: 2 AN: 134336 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000311

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 8 AN: 481706 Hom.: 0 AF XY: 0.0000118 AC XY: 3 AN XY: 253392

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000501

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000161

Gnomad4 OTH exome AF: 0.0000384

GnomAD4 genome AF: 0.0000149 AC: 2 AN: 134336 Hom.: 0 Cov.: 0 AF XY: 0.0000158 AC XY: 1 AN XY: 63348

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000311

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;