rs2252893

Variant names:

• chr21-37135272-T-C
• rs2252893
• NM_001330683.2:c.1444-108T>C

Variant summary

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

The NM_001330683.2(TTC3):​c.1444-108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,246,762 control chromosomes in the GnomAD database, including 150,036 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 0.53 (22171 hom., cov: 32)
  • Exomes 𝑓: 0.48 (127865 hom.)
• Consequence: TTC3 NM_001330683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC3	NM_001330683.2	c.1444-108T>C		intron_variant	Intron 17 of 45	ENST00000418766.6	NP_001317612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC3	ENST00000418766.6	c.1444-108T>C		intron_variant	Intron 17 of 45	5	NM_001330683.2	ENSP00000403943.2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80836 AN: 151830 Hom.: 22139 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.481 AC: 526071 AN: 1094814 Hom.: 127865 AF XY: 0.482 AC XY: 260263 AN XY: 539428

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.533 AC: 80915 AN: 151948 Hom.: 22171 Cov.: 32 AF XY: 0.535 AC XY: 39747 AN XY: 74246

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.547

Alfa AF: 0.481 Hom.: 8847

Bravo AF: 0.536

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.47

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: rs2252893; hg19: chr21-38507572;