5-40679743-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000637375.1(TTC33):c.221+67055T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,116 control chromosomes in the GnomAD database, including 16,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16782 hom., cov: 30)
  • Exomes 𝑓: 0.61 (19 hom.)
• Consequence: TTC33 ENST00000637375.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790

Genes affected

TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-40679743-A-G is Benign according to our data. Variant chr5-40679743-A-G is described in ClinVar as [Benign]. Clinvar id is 1234730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC33	ENST00000636106.1	c.222-66362T>C		intron_variant		5
TTC33	ENST00000636863.1	c.221+67055T>C		intron_variant		5
TTC33	ENST00000637375.1	c.221+67055T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68813 AN: 150908 Hom.: 16777 Cov.: 30

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.610 AC: 61 AN: 100 Hom.: 19 Cov.: 0 AF XY: 0.563 AC XY: 36 AN XY: 64

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.667

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.456 AC: 68834 AN: 151016 Hom.: 16782 Cov.: 30 AF XY: 0.456 AC XY: 33654 AN XY: 73744

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.428

Alfa AF: 0.503 Hom.: 2416

Bravo AF: 0.441

Asia WGS AF: 0.341 AC: 1178 AN: 3456

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

Feb 18, 2020

This variant is associated with the following publications: (PMID: 22695889) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.7
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs45613037; hg19: chr5-40679845;