5-160063240-T-C

Position:

• chr5-160063240-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC1	NM_003314.3	c.746-1692T>C		intron_variant		ENST00000231238.10	NP_003305.1
TTC1	NM_001282500.2	c.746-1692T>C		intron_variant			NP_001269429.1
PWWP2A	XM_011534424.4	c.1566+417A>G		intron_variant			XP_011532726.1
PWWP2A	XR_007058578.1	n.1743+302A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC1	ENST00000231238.10	c.746-1692T>C		intron_variant		1	NM_003314.3	ENSP00000231238	P1

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

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.754

Alfa AF: 0.746 Hom.: 69689

Bravo AF: 0.764

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.74
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs6861719; hg19: chr5-159490247;