rs6556466

Positions:

• chr5-160056134-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.745+4951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,246 control chromosomes in the GnomAD database, including 468 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 0.072 (468 hom., cov: 33)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC1	NM_003314.3	c.745+4951T>C		intron_variant		ENST00000231238.10
TTC1	NM_001282500.2	c.745+4951T>C		intron_variant
PWWP2A	XM_011534424.4	c.1566+7523A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC1	ENST00000231238.10	c.745+4951T>C		intron_variant		1	NM_003314.3	P1

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10877 AN: 152128 Hom.: 460 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0717 AC: 10920 AN: 152246 Hom.: 468 Cov.: 33 AF XY: 0.0702 AC XY: 5224 AN XY: 74464

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0859

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0479

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0584 Hom.: 59

Bravo AF: 0.0784

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.74

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: rs6556466; hg19: chr5-159483141;