GeneBe

2-44942323-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005413.4(SIX3):​c.219C>A​(p.Pro73Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,654 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. P73P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SIX3
NM_005413.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Publications

0 publications found
Variant links:
Genes affected
SIX3 (HGNC:10889): (SIX homeobox 3) This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]
SIX3-AS1 (HGNC:40532): (SIX3 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIX3NM_005413.4 linkc.219C>A p.Pro73Pro synonymous_variant Exon 1 of 2 ENST00000260653.5 NP_005404.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIX3ENST00000260653.5 linkc.219C>A p.Pro73Pro synonymous_variant Exon 1 of 2 1 NM_005413.4 ENSP00000260653.3
ENSG00000225156ENST00000760330.1 linkn.135+7947C>A intron_variant Intron 1 of 1
SIX3-AS1ENST00000760560.1 linkn.389-1490G>T intron_variant Intron 1 of 1
SIX3-AS1ENST00000760561.1 linkn.366-1490G>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1441654
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
717162
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33354
American (AMR)
AF:
0.00
AC:
0
AN:
44430
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26022
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39496
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85950
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
37028
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5688
European-Non Finnish (NFE)
AF:
9.01e-7
AC:
1
AN:
1109740
Other (OTH)
AF:
0.00
AC:
0
AN:
59946
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
13
DANN
Benign
0.97
PhyloP100
1.1
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs186163123; hg19: chr2-45169462; API