rs2032088

Variant names:

• chr21-37105030-G-A
• rs2032088
• NM_001330683.2:c.846-3362G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TTC3	NM_001330683.2	c.846-3362G>A		intron_variant	Intron 10 of 45	ENST00000418766.6	NP_001317612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC3	ENST00000418766.6	c.846-3362G>A		intron_variant	Intron 10 of 45	5	NM_001330683.2	ENSP00000403943.2

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

African (AFR) AF: 0.679 AC: 28165 AN: 41486

American (AMR) AF: 0.692 AC: 10577 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2335 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2407 AN: 5152

South Asian (SAS) AF: 0.469 AC: 2261 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6729 AN: 10550

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45240 AN: 67960

Other (OTH) AF: 0.627 AC: 1320 AN: 2104

Alfa AF: 0.655 Hom.: 18176

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
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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