Variant 19-45765170-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_StrongBA1

The NM_175875.5(SIX5):c.*331C>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 0.0112 in 450,142 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 172 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 45 hom. )

Consequence

SIX5
NM_175875.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0980

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:

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=-0.78).

BP6

Variant 19-45765170-G-A is Benign according to our data. Variant chr19-45765170-G-A is described in ClinVar as [Benign]. Clinvar id is 1271737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIX5	NM_175875.5 linkuse as main transcript	c.*331C>T		3_prime_UTR_variant	3/3	ENST00000317578.7	NP_787071.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SIX5	ENST00000317578.7 linkuse as main transcript	c.*331C>T	3_prime_UTR_variant	3/3	1	NM_175875.5	ENSP00000316842	P1
	ENST00000559756.1 linkuse as main transcript	n.386G>A	non_coding_transcript_exon_variant	1/2	3
SIX5	ENST00000560160.1 linkuse as main transcript	c.*761C>T	3_prime_UTR_variant	2/2	2		ENSP00000453239

Frequencies

GnomAD3 genomes

AF:

0.0261

AC:

3970

AN:

152218

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.00349

AC:

1039

AN:

297806

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

472

AN XY:

156644

show subpopulations

Gnomad4 AFR exome

AF:

0.0953

Gnomad4 AMR exome

AF:

0.00546

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000208

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.0262

AC:

3984

AN:

152336

Hom.:

172

Cov.:

AF XY:

0.0246

AC XY:

1836

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0913

Gnomad4 AMR

AF:

0.00862

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0206

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.00577

AC:

AN:

3478

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	Dec 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.8

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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