rs1344046

Variant names:

• chr21-37144840-A-G
• rs1344046
• NM_001330683.2:c.1893+195A>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.1893+195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,042 control chromosomes in the GnomAD database, including 8,512 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 0.33 (8512 hom., cov: 32)
• Consequence: TTC3 NM_001330683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 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.1893+195A>G		intron	N/A	NP_001317612.1
	TTC3	NM_001320703.2		c.1959+195A>G		intron	N/A	NP_001307632.1
	TTC3	NM_001320704.2		c.1893+195A>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.1893+195A>G		intron	N/A	ENSP00000403943.2
	TTC3	ENST00000354749.6	TSL:1	c.1893+195A>G		intron	N/A	ENSP00000346791.2
	TTC3	ENST00000399017.6	TSL:1	c.1893+195A>G		intron	N/A	ENSP00000381981.2

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49785 AN: 151924 Hom.: 8500 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.328 AC: 49823 AN: 152042 Hom.: 8512 Cov.: 32 AF XY: 0.332 AC XY: 24651 AN XY: 74320

African (AFR) AF: 0.319 AC: 13245 AN: 41464

American (AMR) AF: 0.278 AC: 4249 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1133 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2639 AN: 5164

South Asian (SAS) AF: 0.522 AC: 2520 AN: 4824

European-Finnish (FIN) AF: 0.345 AC: 3640 AN: 10552

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21263 AN: 67972

Other (OTH) AF: 0.367 AC: 775 AN: 2110

Alfa AF: 0.315 Hom.: 995

Bravo AF: 0.319

Asia WGS AF: 0.515 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-0.026
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1344046; hg19: chr21-38517140;