rs1003719

Positions:

• chr21-37118795-A-G
• chr21-37118795-A-T
• chr21-37118795-A-C

Variant summary

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

The NM_001330683.2(TTC3):​c.901-3022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,884 control chromosomes in the GnomAD database, including 18,211 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 0.48 (18211 hom., cov: 31)
• Consequence: TTC3 NM_001330683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC3	NM_001330683.2	c.901-3022A>G		intron_variant		ENST00000418766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC3	ENST00000418766.6	c.901-3022A>G		intron_variant		5	NM_001330683.2	P2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72865 AN: 151766 Hom.: 18196 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.480 AC: 72906 AN: 151884 Hom.: 18211 Cov.: 31 AF XY: 0.476 AC XY: 35340 AN XY: 74222

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.485

Alfa AF: 0.543 Hom.: 35110

Bravo AF: 0.476

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.74

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: rs1003719; hg19: chr21-38491095;