5-160062543-T-C

Variant names:

• chr5-160062543-T-C
• rs3733869
• NM_003314.3:c.746-2389T>C

Variant summary

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

The NM_003314.3(TTC1):​c.746-2389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,090 control chromosomes in the GnomAD database, including 33,163 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 0.66 (33163 hom., cov: 32)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 3 publications found

Genes affected

TTC1 (HGNC:12391): (tetratricopeptide repeat domain 1) This gene encodes a protein that belongs to the tetratrico peptide repeat superfamily of proteins. The encoded protein plays a role in protein-protein interactions, and binds to the Galpha subunit of G protein-coupled receptors to activate the Ras signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

PWWP2A (HGNC:29406): (PWWP domain containing 2A) Enables chromatin binding activity and histone binding activity. Located in nucleus. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003314.3. 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
	TTC1	NM_003314.3	MANE Select	c.746-2389T>C		intron	N/A	NP_003305.1
	TTC1	NM_001282500.2		c.746-2389T>C		intron	N/A	NP_001269429.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC1	ENST00000231238.10	TSL:1 MANE Select	c.746-2389T>C		intron	N/A	ENSP00000231238.4
	TTC1	ENST00000522793.5	TSL:5	c.746-2389T>C		intron	N/A	ENSP00000429225.1
	TTC1	ENST00000682719.1		c.746-2389T>C		intron	N/A	ENSP00000507891.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100315 AN: 151972 Hom.: 33133 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.660 AC: 100399 AN: 152090 Hom.: 33163 Cov.: 32 AF XY: 0.663 AC XY: 49280 AN XY: 74338

African (AFR) AF: 0.671 AC: 27857 AN: 41506

American (AMR) AF: 0.609 AC: 9298 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2546 AN: 3466

East Asian (EAS) AF: 0.725 AC: 3742 AN: 5158

South Asian (SAS) AF: 0.710 AC: 3425 AN: 4826

European-Finnish (FIN) AF: 0.707 AC: 7479 AN: 10584

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43845 AN: 67956

Other (OTH) AF: 0.645 AC: 1359 AN: 2108

Alfa AF: 0.650 Hom.: 85738

Bravo AF: 0.655

Asia WGS AF: 0.718 AC: 2498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.8
DANN	Benign	0.70
PhyloP100		-0.27
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: rs3733869; hg19: chr5-159489550;