NM_001025356.3:c.102C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001025356.3(ANO6):​c.102C>T​(p.Pro34Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,613,810 control chromosomes in the GnomAD database, including 927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 479 hom., cov: 33)
Exomes 𝑓: 0.0049 ( 448 hom. )

Consequence

ANO6
NM_001025356.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.338

Publications

5 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 12-45302045-C-T is Benign according to our data. Variant chr12-45302045-C-T is described in ClinVar as [Benign]. Clinvar id is 257139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.338 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANO6NM_001025356.3 linkc.102C>T p.Pro34Pro synonymous_variant Exon 2 of 20 ENST00000320560.13 NP_001020527.2 Q4KMQ2-1B3KX12

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANO6ENST00000320560.13 linkc.102C>T p.Pro34Pro synonymous_variant Exon 2 of 20 1 NM_001025356.3 ENSP00000320087.8 Q4KMQ2-1

Frequencies

GnomAD3 genomes
AF:
0.0439
AC:
6677
AN:
152022
Hom.:
479
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.149
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0260
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000779
Gnomad OTH
AF:
0.0354
GnomAD2 exomes
AF:
0.0121
AC:
3037
AN:
251294
AF XY:
0.00826
show subpopulations
Gnomad AFR exome
AF:
0.158
Gnomad AMR exome
AF:
0.00869
Gnomad ASJ exome
AF:
0.00149
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000818
Gnomad OTH exome
AF:
0.00620
GnomAD4 exome
AF:
0.00493
AC:
7211
AN:
1461670
Hom.:
448
Cov.:
32
AF XY:
0.00422
AC XY:
3065
AN XY:
727140
show subpopulations
African (AFR)
AF:
0.159
AC:
5312
AN:
33466
American (AMR)
AF:
0.00984
AC:
440
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00122
AC:
32
AN:
26124
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39690
South Asian (SAS)
AF:
0.000939
AC:
81
AN:
86258
European-Finnish (FIN)
AF:
0.000262
AC:
14
AN:
53416
Middle Eastern (MID)
AF:
0.0109
AC:
63
AN:
5766
European-Non Finnish (NFE)
AF:
0.000522
AC:
580
AN:
1111864
Other (OTH)
AF:
0.0114
AC:
688
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
331
662
992
1323
1654
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
170
340
510
680
850
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0440
AC:
6699
AN:
152140
Hom.:
479
Cov.:
33
AF XY:
0.0422
AC XY:
3141
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.149
AC:
6163
AN:
41460
American (AMR)
AF:
0.0259
AC:
396
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.000865
AC:
3
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.000414
AC:
2
AN:
4826
European-Finnish (FIN)
AF:
0.000189
AC:
2
AN:
10594
Middle Eastern (MID)
AF:
0.0204
AC:
6
AN:
294
European-Non Finnish (NFE)
AF:
0.000779
AC:
53
AN:
68022
Other (OTH)
AF:
0.0350
AC:
74
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
291
582
873
1164
1455
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
62
124
186
248
310
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0205
Hom.:
140
Bravo
AF:
0.0516
Asia WGS
AF:
0.00982
AC:
34
AN:
3478
EpiCase
AF:
0.00131
EpiControl
AF:
0.000889

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nov 10, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
8.1
DANN
Benign
0.48
PhyloP100
-0.34
Mutation Taster
=97/3
polymorphism (auto)

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

Publications

Other links and lift over

dbSNP: rs7299561; hg19: chr12-45695828; API