8-58851809-CAATAAATA-C

Position:

• chr8-58851809-CAATAAATA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014729.3(TOX):​c.412-12_412-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,182,654 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0034 (16 hom.)
• Consequence: TOX NM_014729.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75

Genes affected

TOX (HGNC:18988): (thymocyte selection associated high mobility group box) The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-58851809-CAATAAATA-C is Benign according to our data. Variant chr8-58851809-CAATAAATA-C is described in ClinVar as [Benign]. Clinvar id is 774882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00342 (3549/1036280) while in subpopulation AFR AF= 0.0185 (392/21226). AF 95% confidence interval is 0.017. There are 16 homozygotes in gnomad4_exome. There are 1665 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX	NM_014729.3	c.412-12_412-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX	ENST00000361421.2	c.412-12_412-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014729.3	P1

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 788 AN: 146276 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00160

Gnomad SAS AF: 0.00459

Gnomad FIN AF: 0.000960

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00902

GnomAD3 exomes AF: 0.00239 AC: 259 AN: 108206 Hom.: 9 AF XY: 0.00249 AC XY: 150 AN XY: 60322

Gnomad AFR exome AF: 0.00812

Gnomad AMR exome AF: 0.00563

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.000735

Gnomad SAS exome AF: 0.00242

Gnomad FIN exome AF: 0.00197

Gnomad NFE exome AF: 0.00148

Gnomad OTH exome AF: 0.00335

GnomAD4 exome AF: 0.00342 AC: 3549 AN: 1036280 Hom.: 16 AF XY: 0.00331 AC XY: 1665 AN XY: 502478

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.00579

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.00256

Gnomad4 SAS exome AF: 0.00332

Gnomad4 FIN exome AF: 0.00382

Gnomad4 NFE exome AF: 0.00302

Gnomad4 OTH exome AF: 0.00405

GnomAD4 genome AF: 0.00539 AC: 789 AN: 146374 Hom.: 4 Cov.: 0 AF XY: 0.00536 AC XY: 382 AN XY: 71224

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00160

Gnomad4 SAS AF: 0.00438

Gnomad4 FIN AF: 0.000960

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.00942

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

Invitae

Sep 03, 2018

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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: rs3837195; hg19: chr8-59764368;