rs2252893

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330683.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC3	NM_001330683.2	MANE Select	c.1444-108T>C		intron	N/A	NP_001317612.1
	TTC3	NM_001320703.2		c.1510-108T>C		intron	N/A	NP_001307632.1
	TTC3	NM_001320704.2		c.1444-108T>C		intron	N/A	NP_001307633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC3	ENST00000418766.6	TSL:5 MANE Select	c.1444-108T>C		intron	N/A	ENSP00000403943.2
	TTC3	ENST00000354749.6	TSL:1	c.1444-108T>C		intron	N/A	ENSP00000346791.2
	TTC3	ENST00000399017.6	TSL:1	c.1444-108T>C		intron	N/A	ENSP00000381981.2

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

African (AFR) AF: 0.653 AC: 15984 AN: 24480

American (AMR) AF: 0.597 AC: 12682 AN: 21242

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 7464 AN: 18262

East Asian (EAS) AF: 0.575 AC: 19469 AN: 33886

South Asian (SAS) AF: 0.585 AC: 33876 AN: 57874

European-Finnish (FIN) AF: 0.541 AC: 24391 AN: 45082

Middle Eastern (MID) AF: 0.479 AC: 1538 AN: 3212

European-Non Finnish (NFE) AF: 0.459 AC: 387499 AN: 843900

Other (OTH) AF: 0.494 AC: 23168 AN: 46876

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

African (AFR) AF: 0.638 AC: 26415 AN: 41424

American (AMR) AF: 0.579 AC: 8850 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3466

East Asian (EAS) AF: 0.572 AC: 2958 AN: 5170

South Asian (SAS) AF: 0.581 AC: 2799 AN: 4820

European-Finnish (FIN) AF: 0.535 AC: 5632 AN: 10518

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31256 AN: 67958

Other (OTH) AF: 0.547 AC: 1156 AN: 2114

Alfa AF: 0.481 Hom.: 10058

Bravo AF: 0.536

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.70
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: rs2252893; hg19: chr21-38507572;