chr11-26559733-C-T

Variant names:

• chr11-26559733-C-T
• rs149918645
• NM_031418.4:c.1401C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_031418.4(ANO3):​c.1401C>T​(p.Phe467Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,610,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ANO3 NM_031418.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34
• Publications: 0 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]

MUC15 (HGNC:14956): (mucin 15, cell surface associated) Predicted to be located in Golgi lumen and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-26559733-C-T is Benign according to our data. Variant chr11-26559733-C-T is described in ClinVar as Benign. ClinVar VariationId is 696089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000718 (109/151800) while in subpopulation AFR AF = 0.00239 (99/41440). AF 95% confidence interval is 0.00201. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 109 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.1401C>T	p.Phe467Phe	synonymous	Exon 14 of 27	NP_113606.2	Q9BYT9-1
	MUC15	NM_001135091.2	MANE Select	c.*1332G>A		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_001313726.2		c.1584C>T	p.Phe528Phe	synonymous	Exon 15 of 28	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.1401C>T	p.Phe467Phe	synonymous	Exon 14 of 27	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000529533.6	TSL:1 MANE Select	c.*1332G>A		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000672621.1		c.1584C>T	p.Phe528Phe	synonymous	Exon 15 of 28	ENSP00000500506.1	A0A5F9ZHL6

Frequencies

GnomAD3 genomes AF: 0.000719 AC: 109 AN: 151684 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000251 AC: 63 AN: 251278 AF XY: 0.000214

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000101 AC: 148 AN: 1458502 Hom.: 0 Cov.: 29 AF XY: 0.0000951 AC XY: 69 AN XY: 725796

African (AFR) AF: 0.00189 AC: 63 AN: 33402

American (AMR) AF: 0.000112 AC: 5 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.0000759 AC: 3 AN: 39540

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86174

European-Finnish (FIN) AF: 0.0000564 AC: 3 AN: 53228

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5686

European-Non Finnish (NFE) AF: 0.0000532 AC: 59 AN: 1109506

Other (OTH) AF: 0.000183 AC: 11 AN: 60230

GnomAD4 genome AF: 0.000718 AC: 109 AN: 151800 Hom.: 0 Cov.: 32 AF XY: 0.000607 AC XY: 45 AN XY: 74170

African (AFR) AF: 0.00239 AC: 99 AN: 41440

American (AMR) AF: 0.000329 AC: 5 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000642 Hom.: 0

Bravo AF: 0.000952

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.3
Mutation Taster		=94/6	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: rs149918645; hg19: chr11-26581280; COSMIC: COSV99846340; COSMIC: COSV99846340;