rs2032088

chr21-37105030-G-A

Variant summary

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

The NM_001330683.2(TTC3):c.846-3362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,038 control chromosomes in the GnomAD database, including 33,078 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 0.66 (33078 hom., cov: 31)
• Consequence: TTC3 NM_001330683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

Genes affected

TTC3 (HGNC:12393): (tetratricopeptide repeat domain 3) Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC3	NM_001330683.2	c.846-3362G>A		intron_variant		ENST00000418766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC3	ENST00000418766.6	c.846-3362G>A		intron_variant		5	NM_001330683.2	P2

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99788 AN: 151920 Hom.: 33043 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.657 AC: 99868 AN: 152038 Hom.: 33078 Cov.: 31 AF XY: 0.652 AC XY: 48476 AN XY: 74306

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.627

Alfa AF: 0.654 Hom.: 16294

Bravo AF: 0.664

Asia WGS AF: 0.470 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.32
Dann	Benign	0.35

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: rs2032088; hg19: chr21-38477330; COSMIC: COSV100694958; COSMIC: COSV100694958;