11-26332133-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031418.4(ANO3):c.-143G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,517,534 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (9 hom., cov: 30)
  • Exomes 𝑓: 0.00057 (6 hom.)
• Consequence: ANO3 NM_031418.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.416

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-26332133-G-A is Benign according to our data. Variant chr11-26332133-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00576 (877/152304) while in subpopulation AFR AF= 0.0205 (851/41570). AF 95% confidence interval is 0.0193. There are 9 homozygotes in gnomad4. There are 427 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 873 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.-143G>A		5_prime_UTR_variant	1/27	ENST00000256737.8
ANO3	XM_047427399.1	c.-143G>A		5_prime_UTR_variant	1/26
ANO3	NM_001313726.2	c.229+22414G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.-143G>A		5_prime_UTR_variant	1/27	1	NM_031418.4	P3
ANO3	ENST00000531646.1	c.-143G>A		5_prime_UTR_variant	1/5	4
ANO3	ENST00000525139.5	c.-3+22414G>A		intron_variant		5
ANO3	ENST00000672621.1	c.229+22414G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152186 Hom.: 9 Cov.: 30

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000566 AC: 773 AN: 1365230 Hom.: 6 Cov.: 32 AF XY: 0.000517 AC XY: 347 AN XY: 671188

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000938

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00576 AC: 877 AN: 152304 Hom.: 9 Cov.: 30 AF XY: 0.00573 AC XY: 427 AN XY: 74472

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.00656

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	9.9
Dann	Benign	0.83

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: rs114059269; hg19: chr11-26353680;