Variant 19-45765396-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_175875.5(SIX5):c.*105C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 1,523,012 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 121 hom. )

Consequence

SIX5
NM_175875.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0180

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]

SIX5 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-45765396-G-A is Benign according to our data. Variant chr19-45765396-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1318431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00663 (1010/152300) while in subpopulation SAS AF= 0.0221 (107/4832). AF 95% confidence interval is 0.0187. There are 9 homozygotes in gnomad4. There are 510 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1010 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIX5	NM_175875.5 linkuse as main transcript	c.*105C>T		3_prime_UTR_variant	3/3	ENST00000317578.7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
SIX5	ENST00000317578.7 linkuse as main transcript	c.*105C>T	3_prime_UTR_variant	3/3	1	NM_175875.5	P1
	ENST00000559756.1 linkuse as main transcript	n.612G>A	non_coding_transcript_exon_variant	1/2	3
SIX5	ENST00000560160.1 linkuse as main transcript	c.*535C>T	3_prime_UTR_variant	2/2	2
SIX5	ENST00000560168.1 linkuse as main transcript	c.*1751C>T	3_prime_UTR_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.00663

AC:

1009

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0223

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00691

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.00809

AC:

11092

AN:

1370712

Hom.:

121

Cov.:

AF XY:

0.00862

AC XY:

5918

AN XY:

686606

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.00890

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0248

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00612

Gnomad4 OTH exome

AF:

0.00768

GnomAD4 genome

AF:

0.00663

AC:

1010

AN:

152300

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0221

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.00691

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00903

Hom.:

Bravo

AF:

0.00606

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over