rs12295638

chr11-26583784-T-Cchr11-26583784-T-G

Variant summary

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

The NM_031418.4(ANO3):c.1448-14581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,158 control chromosomes in the GnomAD database, including 1,038 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 (1038 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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]

LOC124902648 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.1448-14581T>C		intron_variant		ENST00000256737.8
LOC124902648	XR_007062627.1	n.780A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.1448-14581T>C		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.1400-14581T>C		intron_variant		5
ANO3	ENST00000531568.1	c.1010-14581T>C		intron_variant		2		A1
ANO3	ENST00000672621.1	c.1631-14581T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16180 AN: 152040 Hom.: 1037 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0970

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.106 AC: 16195 AN: 152158 Hom.: 1038 Cov.: 32 AF XY: 0.108 AC XY: 8067 AN XY: 74382

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.0801

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0970

Gnomad4 OTH AF: 0.105

Alfa AF: 0.104 Hom.: 2157

Bravo AF: 0.109

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.7
Dann	Benign	0.73

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: rs12295638; hg19: chr11-26605331;