rs2835621

chr21-37138316-G-A

Variant summary

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

The NM_001330683.2(TTC3):c.1579-318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,038 control chromosomes in the GnomAD database, including 22,248 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 (22248 hom., cov: 32)
• Consequence: TTC3 NM_001330683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC3	NM_001330683.2	c.1579-318G>A		intron_variant		ENST00000418766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC3	ENST00000418766.6	c.1579-318G>A		intron_variant		5	NM_001330683.2	P2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80980 AN: 151920 Hom.: 22216 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.533 AC: 81057 AN: 152038 Hom.: 22248 Cov.: 32 AF XY: 0.536 AC XY: 39807 AN XY: 74294

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.547

Alfa AF: 0.475 Hom.: 11576

Bravo AF: 0.536

Asia WGS AF: 0.597 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
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: rs2835621; hg19: chr21-38510616;