19-45765469-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175875.5(SIX5):​c.*32T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,612,812 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00039 ( 3 hom. )

Consequence

SIX5
NM_175875.5 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0150
Variant links:
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 19-45765469-A-G is Benign according to our data. Variant chr19-45765469-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317909.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 594 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SIX5NM_175875.5 linkuse as main transcriptc.*32T>C 3_prime_UTR_variant 3/3 ENST00000317578.7 NP_787071.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SIX5ENST00000317578.7 linkuse as main transcriptc.*32T>C 3_prime_UTR_variant 3/31 NM_175875.5 ENSP00000316842 P1
ENST00000559756.1 linkuse as main transcriptn.685A>G non_coding_transcript_exon_variant 1/23
SIX5ENST00000560160.1 linkuse as main transcriptc.*462T>C 3_prime_UTR_variant 2/22 ENSP00000453239
SIX5ENST00000560168.1 linkuse as main transcriptc.*1678T>C 3_prime_UTR_variant 3/34 ENSP00000453189

Frequencies

GnomAD3 genomes
AF:
0.00388
AC:
590
AN:
152124
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0134
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00177
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000896
AC:
225
AN:
251074
Hom.:
1
AF XY:
0.000633
AC XY:
86
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0128
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000389
AC:
568
AN:
1460570
Hom.:
3
Cov.:
29
AF XY:
0.000361
AC XY:
262
AN XY:
726614
show subpopulations
Gnomad4 AFR exome
AF:
0.0144
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.000845
GnomAD4 genome
AF:
0.00390
AC:
594
AN:
152242
Hom.:
6
Cov.:
33
AF XY:
0.00375
AC XY:
279
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0134
Gnomad4 AMR
AF:
0.00176
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000783
Hom.:
0
Bravo
AF:
0.00437
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
12
DANN
Benign
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75443440; hg19: chr19-46268727; API