Variant chr2-44942194-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005413.4(SIX3):c.90G>T(p.Ala30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,596,786 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 64 hom., cov: 31)

Exomes 𝑓: 0.019 ( 614 hom. )

Consequence

SIX3
NM_005413.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

SIX3 (HGNC:10889): (SIX homeobox 3) This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]

SIX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 2-44942194-G-T is Benign according to our data. Variant chr2-44942194-G-T is described in ClinVar as [Benign]. Clinvar id is 65505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIX3	NM_005413.4 linkuse as main transcript	c.90G>T	p.Ala30=	synonymous_variant	1/2	ENST00000260653.5	NP_005404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIX3	ENST00000260653.5 linkuse as main transcript	c.90G>T	p.Ala30=	synonymous_variant	1/2	1	NM_005413.4	ENSP00000260653	P1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3103

AN:

151380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00918

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0574

Gnomad ASJ

AF:

0.0689

Gnomad EAS

AF:

0.0498

Gnomad SAS

AF:

0.0438

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.0385

GnomAD3 exomes

AF:

0.0354

AC:

8294

AN:

234134

Hom.:

304

AF XY:

0.0338

AC XY:

4338

AN XY:

128228

show subpopulations

Gnomad AFR exome

AF:

0.00948

Gnomad AMR exome

AF:

0.0932

Gnomad ASJ exome

AF:

0.0734

Gnomad EAS exome

AF:

0.0529

Gnomad SAS exome

AF:

0.0447

Gnomad FIN exome

AF:

0.00882

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0346

GnomAD4 exome

AF:

0.0191

AC:

27641

AN:

1445294

Hom.:

614

Cov.:

AF XY:

0.0200

AC XY:

14403

AN XY:

719418

show subpopulations

Gnomad4 AFR exome

AF:

0.00854

Gnomad4 AMR exome

AF:

0.0894

Gnomad4 ASJ exome

AF:

0.0765

Gnomad4 EAS exome

AF:

0.0380

Gnomad4 SAS exome

AF:

0.0457

Gnomad4 FIN exome

AF:

0.00739

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0249

GnomAD4 genome

AF:

0.0205

AC:

3105

AN:

151492

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1604

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.00922

Gnomad4 AMR

AF:

0.0576

Gnomad4 ASJ

AF:

0.0689

Gnomad4 EAS

AF:

0.0498

Gnomad4 SAS

AF:

0.0438

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.0381

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

EpiCase

AF:

0.0195

EpiControl

AF:

0.0212

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 32022405) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 14, 2017	- -

Holoprosencephaly 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, no assertion criteria provided	curation	GeneReviews	Aug 29, 2013	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

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