rs10515803

chr5-160047858-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003314.3(TTC1):c.542-1656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 151,956 control chromosomes in the GnomAD database, including 695 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 0.081 (695 hom., cov: 32)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC1	NM_003314.3	c.542-1656G>A		intron_variant		ENST00000231238.10
TTC1	NM_001282500.2	c.542-1656G>A		intron_variant
PWWP2A	XM_011534424.4	c.1567-2599C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC1	ENST00000231238.10	c.542-1656G>A		intron_variant		1	NM_003314.3	P1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12361 AN: 151838 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0983

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

GnomAD4 genome AF: 0.0813 AC: 12356 AN: 151956 Hom.: 695 Cov.: 32 AF XY: 0.0825 AC XY: 6128 AN XY: 74250

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0753

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0977

Alfa AF: 0.0926 Hom.: 145

Bravo AF: 0.0899

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.12
Dann	Benign	0.75

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: rs10515803; hg19: chr5-159474865; COSMIC: COSV51464435;