NM_001330683.2:c.2119-536A>G

Variant names:

• chr21-37149542-A-G
• rs2835630
• NM_001330683.2:c.2119-536A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330683.2(TTC3):​c.2119-536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,998 control chromosomes in the GnomAD database, including 23,101 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 0.54 (23101 hom., cov: 32)
• Consequence: TTC3 NM_001330683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 13 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 (AFR) allele frequency at 95% confidence interval = 0.64 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.2119-536A>G		intron	N/A	NP_001317612.1
	TTC3	NM_001320703.2		c.2185-536A>G		intron	N/A	NP_001307632.1
	TTC3	NM_001320704.2		c.2119-536A>G		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.2119-536A>G		intron	N/A	ENSP00000403943.2
	TTC3	ENST00000354749.6	TSL:1	c.2119-536A>G		intron	N/A	ENSP00000346791.2
	TTC3	ENST00000399017.6	TSL:1	c.2119-536A>G		intron	N/A	ENSP00000381981.2

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82631 AN: 151880 Hom.: 23066 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.544 AC: 82716 AN: 151998 Hom.: 23101 Cov.: 32 AF XY: 0.548 AC XY: 40708 AN XY: 74302

African (AFR) AF: 0.646 AC: 26771 AN: 41424

American (AMR) AF: 0.584 AC: 8920 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3115 AN: 5166

South Asian (SAS) AF: 0.594 AC: 2859 AN: 4810

European-Finnish (FIN) AF: 0.566 AC: 5978 AN: 10566

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32033 AN: 67968

Other (OTH) AF: 0.553 AC: 1166 AN: 2108

Alfa AF: 0.470 Hom.: 11807

Bravo AF: 0.545

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.34
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: rs2835630; hg19: chr21-38521842;