19-45765456-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_175875.5(SIX5):c.*45G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,612,082 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.027 ( 187 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 196 hom. )
Consequence
SIX5
NM_175875.5 3_prime_UTR
NM_175875.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.639
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 19-45765456-C-T is Benign according to our data. Variant chr19-45765456-C-T is described in ClinVar as [Benign]. Clinvar id is 1251781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIX5 | NM_175875.5 | c.*45G>A | 3_prime_UTR_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.*45G>A | 3_prime_UTR_variant | 3/3 | 1 | NM_175875.5 | ENSP00000316842 | P1 | ||
ENST00000559756.1 | n.672C>T | non_coding_transcript_exon_variant | 1/2 | 3 | ||||||
SIX5 | ENST00000560160.1 | c.*475G>A | 3_prime_UTR_variant | 2/2 | 2 | ENSP00000453239 | ||||
SIX5 | ENST00000560168.1 | c.*1691G>A | 3_prime_UTR_variant | 3/3 | 4 | ENSP00000453189 |
Frequencies
GnomAD3 genomes AF: 0.0272 AC: 4143AN: 152148Hom.: 186 Cov.: 33
GnomAD3 genomes
AF:
AC:
4143
AN:
152148
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00723 AC: 1812AN: 250782Hom.: 86 AF XY: 0.00500 AC XY: 679AN XY: 135746
GnomAD3 exomes
AF:
AC:
1812
AN:
250782
Hom.:
AF XY:
AC XY:
679
AN XY:
135746
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00272 AC: 3973AN: 1459816Hom.: 196 Cov.: 29 AF XY: 0.00229 AC XY: 1660AN XY: 726268
GnomAD4 exome
AF:
AC:
3973
AN:
1459816
Hom.:
Cov.:
29
AF XY:
AC XY:
1660
AN XY:
726268
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0273 AC: 4157AN: 152266Hom.: 187 Cov.: 33 AF XY: 0.0261 AC XY: 1943AN XY: 74452
GnomAD4 genome
AF:
AC:
4157
AN:
152266
Hom.:
Cov.:
33
AF XY:
AC XY:
1943
AN XY:
74452
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
26
AN:
3476
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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