rs4434423

Positions:

• chr5-40677580-T-A
• chr5-40677580-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637375.1(TTC33):​c.221+69218A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,978 control chromosomes in the GnomAD database, including 29,961 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (29961 hom., cov: 31)
• Consequence: TTC33 ENST00000637375.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.66 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.222-64199A>T		intron_variant		5
TTC33	ENST00000636863.1	c.221+69218A>T		intron_variant		5
TTC33	ENST00000637375.1	c.221+69218A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95177 AN: 151860 Hom.: 29930 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95264 AN: 151978 Hom.: 29961 Cov.: 31 AF XY: 0.625 AC XY: 46392 AN XY: 74278

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.601

Alfa AF: 0.635 Hom.: 3730

Bravo AF: 0.632

Asia WGS AF: 0.546 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4434423; hg19: chr5-40677682;