rs2835582

Variant names:

• chr21-37086473-C-G
• rs2835582
• ENST00000354749:c.-785C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-37086473-C-G
• chr21-37086473-C-T

Variant summary

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

The ENST00000354749(TTC3):​c.-785C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,032 control chromosomes in the GnomAD database, including 16,339 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 0.46 (16333 hom., cov: 32)
  • Exomes 𝑓: 0.73 (6 hom.)
• Consequence: TTC3 ENST00000354749 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC3	NM_001330683.2	c.-11-774C>G		intron_variant	Intron 1 of 45	ENST00000418766.6	NP_001317612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC3	ENST00000418766.6	c.-11-774C>G		intron_variant	Intron 1 of 45	5	NM_001330683.2	ENSP00000403943.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69242 AN: 151892 Hom.: 16317 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.727 AC: 16 AN: 22 Hom.: 6 Cov.: 0 AF XY: 0.778 AC XY: 14 AN XY: 18

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.456 AC: 69283 AN: 152010 Hom.: 16333 Cov.: 32 AF XY: 0.453 AC XY: 33684 AN XY: 74290

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.451

Alfa AF: 0.473 Hom.: 2099

Bravo AF: 0.453

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	8.6
DANN	Benign	0.69

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: rs2835582; hg19: chr21-38458773;