21-37118795-A-G

Variant names:

• chr21-37118795-A-G
• rs1003719
• NM_001330683.2:c.901-3022A>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.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
• Publications: 40 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC3	NM_001330683.2	MANE Select	c.901-3022A>G		intron	N/A	NP_001317612.1	P53804-1
	TTC3	NM_001320703.2		c.967-3022A>G		intron	N/A	NP_001307632.1
	TTC3	NM_001320704.2		c.901-3022A>G		intron	N/A	NP_001307633.1	H7BZ57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC3	ENST00000418766.6	TSL:5 MANE Select	c.901-3022A>G		intron	N/A	ENSP00000403943.2	P53804-1
	TTC3	ENST00000354749.6	TSL:1	c.901-3022A>G		intron	N/A	ENSP00000346791.2	P53804-1
	TTC3	ENST00000399017.6	TSL:1	c.901-3022A>G		intron	N/A	ENSP00000381981.2	P53804-1

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

African (AFR) AF: 0.362 AC: 14991 AN: 41408

American (AMR) AF: 0.441 AC: 6736 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2137 AN: 3466

East Asian (EAS) AF: 0.406 AC: 2097 AN: 5162

South Asian (SAS) AF: 0.439 AC: 2111 AN: 4814

European-Finnish (FIN) AF: 0.484 AC: 5088 AN: 10516

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37933 AN: 67932

Other (OTH) AF: 0.485 AC: 1023 AN: 2108

Alfa AF: 0.533 Hom.: 77557

Bravo AF: 0.476

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.74
PhyloP100		-0.32
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: rs1003719; hg19: chr21-38491095;