chr12-45357362-C-G

Variant names:

• chr12-45357362-C-G
• rs145896287
• NM_001025356.3:c.936C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001025356.3(ANO6):​c.936C>G​(p.Ala312Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A312A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ANO6 NM_001025356.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 0 publications found

Genes affected

ANO6 (HGNC:25240): (anoctamin 6) This gene encodes a multi-pass transmembrane protein that belongs to the anoctamin family. This protein is an essential component for the calcium-dependent exposure of phosphatidylserine on the cell surface. The scrambling of phospholipid occurs in various biological systems, such as when blood platelets are activated, they expose phosphatidylserine to trigger the clotting system. Mutations in this gene are associated with Scott syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

ANO6 Gene-Disease associations (from GenCC):

• Scott syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ENSG00000293678 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.597 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025356.3. 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
	ANO6	NM_001025356.3	MANE Select	c.936C>G	p.Ala312Ala	synonymous	Exon 8 of 20	NP_001020527.2	Q4KMQ2-1
	ANO6	NM_001204803.2		c.999C>G	p.Ala333Ala	synonymous	Exon 9 of 21	NP_001191732.1	Q4KMQ2-2
	ANO6	NM_001142679.2		c.936C>G	p.Ala312Ala	synonymous	Exon 8 of 20	NP_001136151.1	Q4KMQ2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO6	ENST00000320560.13	TSL:1 MANE Select	c.936C>G	p.Ala312Ala	synonymous	Exon 8 of 20	ENSP00000320087.8	Q4KMQ2-1
	ANO6	ENST00000423947.7	TSL:1	c.999C>G	p.Ala333Ala	synonymous	Exon 9 of 21	ENSP00000409126.3	Q4KMQ2-2
	ANO6	ENST00000425752.6	TSL:1	c.936C>G	p.Ala312Ala	synonymous	Exon 8 of 20	ENSP00000391417.2	Q4KMQ2-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461690 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111962

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.010
DANN	Benign	0.54
PhyloP100		-0.60

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: rs145896287; hg19: chr12-45751145;