Variant 19-45767919-G-T 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.803+123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,052,008 control chromosomes in the GnomAD database, including 121,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17269 hom., cov: 34)

Exomes 𝑓: 0.48 ( 104164 hom. )

Consequence

SIX5
NM_175875.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.277

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:

DM1-AS (HGNC:53125): (DM1 locus antisense RNA)

DM1-AS 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=-0.76).

BP6

Variant 19-45767919-G-T is Benign according to our data. Variant chr19-45767919-G-T is described in ClinVar as [Benign]. Clinvar id is 1174287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 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.803+123C>A		intron_variant		ENST00000317578.7	NP_787071.3
DM1-AS	NR_147193.1 linkuse as main transcript	n.124G>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SIX5	ENST00000317578.7 linkuse as main transcript	c.803+123C>A	intron_variant		1	NM_175875.5	ENSP00000316842	P1
DM1-AS	ENST00000590076.2 linkuse as main transcript	n.124G>T	non_coding_transcript_exon_variant	1/2	4
	ENST00000559756.1 linkuse as main transcript	n.1181-913G>T	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71630

AN:

151956

Hom.:

17255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.591

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.481

GnomAD4 exome

AF:

0.475

AC:

427807

AN:

899934

Hom.:

104164

Cov.:

AF XY:

0.479

AC XY:

215279

AN XY:

449638

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.667

Gnomad4 SAS exome

AF:

0.588

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.476

GnomAD4 genome

AF:

0.471

AC:

71684

AN:

152074

Hom.:

17269

Cov.:

AF XY:

0.478

AC XY:

35528

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.592

Gnomad4 ASJ

AF:

0.391

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.595

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.484

Alfa

AF:

0.481

Hom.:

6075

Bravo

AF:

0.480

Asia WGS

AF:

0.595

AC:

2071

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.2

DANN

Benign

0.79

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