2-44941807-TCTCTCC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005413.4(SIX3):c.-280_-275del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 360,230 control chromosomes in the GnomAD database, including 1,072 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (728 hom., cov: 28)
  • Exomes 𝑓: 0.040 (344 hom.)
• Consequence: SIX3 NM_005413.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.734

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-44941807-TCTCTCC-T is Benign according to our data. Variant chr2-44941807-TCTCTCC-T is described in ClinVar as [Benign]. Clinvar id is 1243127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIX3	NM_005413.4	c.-280_-275del		5_prime_UTR_variant	1/2	ENST00000260653.5
SIX3-AS1	NR_103786.1	n.66_71del		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIX3	ENST00000260653.5	c.-280_-275del		5_prime_UTR_variant	1/2	1	NM_005413.4	P1
SIX3-AS1	ENST00000419364.3	n.104_109del		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11866 AN: 151298 Hom.: 705 Cov.: 28

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0525

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0883

GnomAD4 exome AF: 0.0399 AC: 8341 AN: 208812 Hom.: 344 AF XY: 0.0414 AC XY: 4563 AN XY: 110198

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.0763

Gnomad4 ASJ exome AF: 0.0781

Gnomad4 EAS exome AF: 0.0354

Gnomad4 SAS exome AF: 0.0594

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0281

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0788 AC: 11929 AN: 151418 Hom.: 728 Cov.: 28 AF XY: 0.0782 AC XY: 5783 AN XY: 73998

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0524

Gnomad4 SAS AF: 0.0712

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0874

Alfa AF: 0.0147 Hom.: 5

Bravo AF: 0.0893

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 17, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56821771; hg19: chr2-45168946;