chr5-160062448-C-T

Variant names:

• chr5-160062448-C-T
• rs3733868
• NM_003314.3:c.746-2484C>T

Variant summary

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

The NM_003314.3(TTC1):​c.746-2484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,316 control chromosomes in the GnomAD database, including 316 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 0.056 (316 hom., cov: 33)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC1	NM_003314.3	c.746-2484C>T		intron_variant	Intron 7 of 7	ENST00000231238.10	NP_003305.1
TTC1	NM_001282500.2	c.746-2484C>T		intron_variant	Intron 7 of 7		NP_001269429.1
PWWP2A	XM_011534424.4	c.1566+1209G>A		intron_variant	Intron 3 of 3		XP_011532726.1
PWWP2A	XR_007058578.1	n.1743+1094G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC1	ENST00000231238.10	c.746-2484C>T		intron_variant	Intron 7 of 7	1	NM_003314.3	ENSP00000231238.4

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8491 AN: 152196 Hom.: 316 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0557 AC: 8483 AN: 152316 Hom.: 316 Cov.: 33 AF XY: 0.0585 AC XY: 4353 AN XY: 74472

African (AFR) AF: 0.0129 AC: 537 AN: 41578

American (AMR) AF: 0.0532 AC: 814 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.149 AC: 769 AN: 5170

South Asian (SAS) AF: 0.133 AC: 642 AN: 4830

European-Finnish (FIN) AF: 0.0734 AC: 778 AN: 10606

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0654 AC: 4451 AN: 68034

Other (OTH) AF: 0.0591 AC: 125 AN: 2116

Alfa AF: 0.0631 Hom.: 666

Bravo AF: 0.0517

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3733868; hg19: chr5-159489455;