rs2835582

Variant names:

• chr21-37086473-C-G
• rs2835582
• ENST00000479930.5:n.-785C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000479930.5(TTC3):​n.-785C>G variant causes a non coding transcript exon 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 ENST00000479930.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 8 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=-0.98).
• 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.750 AC: 12 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.361 AC: 14970 AN: 41440

American (AMR) AF: 0.418 AC: 6382 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2082 AN: 3466

East Asian (EAS) AF: 0.408 AC: 2109 AN: 5168

South Asian (SAS) AF: 0.421 AC: 2027 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4721 AN: 10536

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35306 AN: 67982

Other (OTH) AF: 0.451 AC: 953 AN: 2112

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
PhyloP100		0.43
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: rs2835582; hg19: chr21-38458773;