Genetic Variant SIX3:c.-280_-275dupCCTCTC (chr2-44941807-T-TCTCTCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005413.4(SIX3):c.-280_-275dupCCTCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 360,394 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SIX3
NM_005413.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.726

Publications

0 publications found

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:

SIX3-AS1 (HGNC:40532): (SIX3 antisense RNA 1)

SIX3-AS1 links:

ENSG00000225156 (HGNC:):

ENSG00000225156 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIX3	NM_005413.4	MANE Select	c.-280_-275dupCCTCTC		5_prime_UTR	Exon 1 of 2	NP_005404.1	O95343
	SIX3-AS1	NR_103786.1		n.66_71dupGGAGAG		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIX3	ENST00000260653.5	TSL:1 MANE Select	c.-280_-275dupCCTCTC	5_prime_UTR	Exon 1 of 2	ENSP00000260653.3	O95343
SIX3-AS1	ENST00000419364.4	TSL:2	n.256_261dupGGAGAG	non_coding_transcript_exon	Exon 1 of 2
SIX3-AS1	ENST00000760562.1		n.19_24dupGGAGAG	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000727

AC:

AN:

151390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

209004

Hom.:

Cov.:

AF XY:

0.0000363

AC XY:

AN XY:

110306

show subpopulations

African (AFR)

AF:

0.000316

AC:

AN:

6338

American (AMR)

AF:

0.0000990

AC:

AN:

10106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5680

East Asian (EAS)

AF:

0.00

AC:

AN:

12074

South Asian (SAS)

AF:

0.00

AC:

AN:

26838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

850

European-Non Finnish (NFE)

AF:

0.0000163

AC:

AN:

123060

Other (OTH)

AF:

0.0000843

AC:

AN:

11856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000727

AC:

AN:

151390

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73918

show subpopulations

African (AFR)

AF:

0.0000487

AC:

AN:

41104

American (AMR)

AF:

0.0000656

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5108

South Asian (SAS)

AF:

0.00

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67834

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-44941807-TCTCTCC-TCTCTCCCTCTCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over