5-160060946-G-A

Variant names:

• chr5-160060946-G-A
• rs7704770
• NM_003314.3:c.746-3986G>A

Variant summary

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

The NM_003314.3(TTC1):​c.746-3986G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,164 control chromosomes in the GnomAD database, including 27,618 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 0.60 (27618 hom., cov: 33)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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.746-3986G>A		intron	N/A	NP_003305.1
	TTC1	NM_001282500.2		c.746-3986G>A		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.746-3986G>A		intron	N/A	ENSP00000231238.4
	TTC1	ENST00000522793.5	TSL:5	c.746-3986G>A		intron	N/A	ENSP00000429225.1
	TTC1	ENST00000682719.1		c.746-3986G>A		intron	N/A	ENSP00000507891.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91611 AN: 152046 Hom.: 27595 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.603 AC: 91684 AN: 152164 Hom.: 27618 Cov.: 33 AF XY: 0.606 AC XY: 45071 AN XY: 74390

African (AFR) AF: 0.593 AC: 24613 AN: 41504

American (AMR) AF: 0.555 AC: 8488 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3219 AN: 5180

South Asian (SAS) AF: 0.603 AC: 2907 AN: 4824

European-Finnish (FIN) AF: 0.686 AC: 7269 AN: 10594

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40835 AN: 67986

Other (OTH) AF: 0.572 AC: 1209 AN: 2114

Alfa AF: 0.597 Hom.: 38803

Bravo AF: 0.594

Asia WGS AF: 0.609 AC: 2121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.51
PhyloP100		-1.4
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: rs7704770; hg19: chr5-159487953;