5-160063240-T-C

Variant names:

• chr5-160063240-T-C
• rs6861719
• NM_003314.3:c.746-1692T>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.746-1692T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,128 control chromosomes in the GnomAD database, including 43,878 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 0.76 (43878 hom., cov: 32)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 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.746-1692T>C		intron	N/A	NP_003305.1
	TTC1	NM_001282500.2		c.746-1692T>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.746-1692T>C		intron	N/A	ENSP00000231238.4
	TTC1	ENST00000522793.5	TSL:5	c.746-1692T>C		intron	N/A	ENSP00000429225.1
	TTC1	ENST00000682719.1		c.746-1692T>C		intron	N/A	ENSP00000507891.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115376 AN: 152010 Hom.: 43832 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.759 AC: 115480 AN: 152128 Hom.: 43878 Cov.: 32 AF XY: 0.762 AC XY: 56674 AN XY: 74380

African (AFR) AF: 0.754 AC: 31292 AN: 41494

American (AMR) AF: 0.801 AC: 12243 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2799 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4497 AN: 5166

South Asian (SAS) AF: 0.819 AC: 3958 AN: 4832

European-Finnish (FIN) AF: 0.778 AC: 8233 AN: 10586

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49974 AN: 67972

Other (OTH) AF: 0.754 AC: 1593 AN: 2112

Alfa AF: 0.745 Hom.: 155918

Bravo AF: 0.764

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.74
DANN	Benign	0.86
PhyloP100		-0.66
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: rs6861719; hg19: chr5-159490247;