rs756121296

Variant names:

• chr11-26559739-T-C
• rs756121296
• NM_031418.4:c.1407T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031418.4(ANO3):​c.1407T>C​(p.Asn469Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,612,180 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: ANO3 NM_031418.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.660
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-26559739-T-C is Benign according to our data. Variant chr11-26559739-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2858419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.66 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 99 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.1407T>C	p.Asn469Asn	synonymous	Exon 14 of 27	NP_113606.2	Q9BYT9-1
	MUC15	NM_001135091.2	MANE Select	c.*1326A>G		3_prime_UTR	Exon 5 of 5	NP_001128563.1	A0A0A0MT67
	ANO3	NM_001313726.2		c.1590T>C	p.Asn530Asn	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.1407T>C	p.Asn469Asn	synonymous	Exon 14 of 27	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000529533.6	TSL:1 MANE Select	c.*1326A>G		3_prime_UTR	Exon 5 of 5	ENSP00000431983.1	A0A0A0MT67
	ANO3	ENST00000672621.1		c.1590T>C	p.Asn530Asn	synonymous	Exon 15 of 28	ENSP00000500506.1	A0A5F9ZHL6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251338 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000678 AC: 99 AN: 1460098 Hom.: 0 Cov.: 29 AF XY: 0.0000661 AC XY: 48 AN XY: 726518

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000873 AC: 97 AN: 1110640

Other (OTH) AF: 0.0000166 AC: 1 AN: 60328

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15238

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000148 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.50
CADD	Benign	6.9
DANN	Benign	0.89
PhyloP100		0.66

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: rs756121296; hg19: chr11-26581286;