chr19-45765655-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_175875.5(SIX5):c.2066C>A(p.Ala689Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIX5
NM_175875.5 missense
NM_175875.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 1.56
Genes affected
SIX5 (HGNC:10891): (SIX homeobox 5) The protein encoded by this gene is a homeodomain-containing transcription factor that appears to function in the regulation of organogenesis. This gene is located downstream of the dystrophia myotonica-protein kinase gene. Mutations in this gene are a cause of branchiootorenal syndrome type 2. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1737116).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIX5 | NM_175875.5 | c.2066C>A | p.Ala689Asp | missense_variant | 3/3 | ENST00000317578.7 | NP_787071.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SIX5 | ENST00000317578.7 | c.2066C>A | p.Ala689Asp | missense_variant | 3/3 | 1 | NM_175875.5 | ENSP00000316842 | P1 | |
ENST00000559756.1 | n.871G>T | non_coding_transcript_exon_variant | 1/2 | 3 | ||||||
SIX5 | ENST00000560160.1 | c.*276C>A | 3_prime_UTR_variant | 2/2 | 2 | ENSP00000453239 | ||||
SIX5 | ENST00000560168.1 | c.*1492C>A | 3_prime_UTR_variant | 3/3 | 4 | ENSP00000453189 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460370Hom.: 0 Cov.: 60 AF XY: 0.00 AC XY: 0AN XY: 726536
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1460370
Hom.:
Cov.:
60
AF XY:
AC XY:
0
AN XY:
726536
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.2066C>A (p.A689D) alteration is located in exon 3 (coding exon 3) of the SIX5 gene. This alteration results from a C to A substitution at nucleotide position 2066, causing the alanine (A) at amino acid position 689 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.
REVEL
Uncertain
Sift
Uncertain
.;D;.
Sift4G
Uncertain
.;D;D
Polyphen
D;D;.
Vest4
0.37, 0.49
MutPred
Gain of loop (P = 0.069);Gain of loop (P = 0.069);.;
MVP
0.88
MPC
0.14
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.