chr11-26332222-C-T

Variant names:

• chr11-26332222-C-T
• rs149195780
• NM_031418.4:c.-54C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031418.4(ANO3):​c.-54C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,998 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (10 hom., cov: 30)
  • Exomes 𝑓: 0.00076 (10 hom.)
• Consequence: ANO3 NM_031418.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55
• Publications: 2 publications found

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]

ANO3-AS1 (HGNC:54190): (ANO3 antisense RNA 1)

LOC105376598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 11-26332222-C-T is Benign according to our data. Variant chr11-26332222-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1191751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00707 (1076/152214) while in subpopulation AFR AF = 0.0242 (1007/41530). AF 95% confidence interval is 0.023. There are 10 homozygotes in GnomAd4. There are 511 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1076 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	NM_031418.4	MANE Select	c.-54C>T		5_prime_UTR	Exon 1 of 27	NP_113606.2	Q9BYT9-1
	ANO3	NM_001313726.2		c.229+22503C>T		intron	N/A	NP_001300655.1	A0A5F9ZHL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.-54C>T		5_prime_UTR	Exon 1 of 27	ENSP00000256737.3	Q9BYT9-1
	ANO3	ENST00000531646.1	TSL:4	c.-54C>T		5_prime_UTR	Exon 1 of 5	ENSP00000435275.1	E9PKW2
	ANO3	ENST00000672621.1		c.229+22503C>T		intron	N/A	ENSP00000500506.1	A0A5F9ZHL6

Frequencies

GnomAD3 genomes AF: 0.00707 AC: 1076 AN: 152096 Hom.: 10 Cov.: 30

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.000761 AC: 1113 AN: 1461784 Hom.: 10 Cov.: 32 AF XY: 0.000652 AC XY: 474 AN XY: 727202

African (AFR) AF: 0.0247 AC: 827 AN: 33474

American (AMR) AF: 0.00168 AC: 75 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5758

European-Non Finnish (NFE) AF: 0.0000908 AC: 101 AN: 1111946

Other (OTH) AF: 0.00167 AC: 101 AN: 60390

GnomAD4 genome AF: 0.00707 AC: 1076 AN: 152214 Hom.: 10 Cov.: 30 AF XY: 0.00687 AC XY: 511 AN XY: 74406

African (AFR) AF: 0.0242 AC: 1007 AN: 41530

American (AMR) AF: 0.00275 AC: 42 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68030

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00481 Hom.: 3

Bravo AF: 0.00798

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		1.6
PromoterAI		0.10	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs149195780; hg19: chr11-26353769;