rs60329053

Variant names:

• chr12-45429252-G-A
• rs60329053
• NM_001025356.3:c.2674G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-45429252-G-A
• chr12-45429252-G-C
• chr12-45429252-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001025356.3(ANO6):​c.2674G>A​(p.Val892Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V892L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANO6 NM_001025356.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• 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: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000293678 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03898418).

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.2674G>A	p.Val892Met	missense	Exon 20 of 20	NP_001020527.2
	ANO6	NM_001204803.2		c.2737G>A	p.Val913Met	missense	Exon 21 of 21	NP_001191732.1
	ANO6	NM_001410973.1		c.2641G>A	p.Val881Met	missense	Exon 20 of 20	NP_001397902.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO6	ENST00000320560.13	TSL:1 MANE Select	c.2674G>A	p.Val892Met	missense	Exon 20 of 20	ENSP00000320087.8
	ANO6	ENST00000423947.7	TSL:1	c.2737G>A	p.Val913Met	missense	Exon 21 of 21	ENSP00000409126.3
	ANO6	ENST00000441606.2	TSL:1	c.2620G>A	p.Val874Met	missense	Exon 20 of 20	ENSP00000413137.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461596 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727098

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.052	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.47
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.059
Sift	Benign	0.68	T
Sift4G	Benign	0.36	T
Polyphen		0.015	B
Vest4		0.083
MutPred		0.38		Gain of disorder (P = 0.0128)
MVP		0.43
MPC		0.22
ClinPred		0.21	T
GERP RS		-2.1
Varity_R		0.026
gMVP		0.21
Mutation Taster		=96/4	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: rs60329053; hg19: chr12-45823035;