11-26557946-C-T

Position:

• chr11-26557946-C-T

Variant summary

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

The NM_031418.4(ANO3):​c.1387-1773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,202 control chromosomes in the GnomAD database, including 59,528 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 0.88 (59528 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.1387-1773C>T		intron_variant		ENST00000256737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.1387-1773C>T		intron_variant		1	NM_031418.4	P3

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133930 AN: 152084 Hom.: 59507 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.880 AC: 133999 AN: 152202 Hom.: 59528 Cov.: 32 AF XY: 0.882 AC XY: 65587 AN XY: 74400

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.911

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.961

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.886

Alfa AF: 0.915 Hom.: 61087

Bravo AF: 0.875

Asia WGS AF: 0.883 AC: 3073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.50

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: rs293966; hg19: chr11-26579493;