5-160020206-A-G

Variant names:

• chr5-160020206-A-G
• rs10515804
• NM_003314.3:c.330+9348A>G

Variant summary

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

The NM_003314.3(TTC1):​c.330+9348A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,150 control chromosomes in the GnomAD database, including 44,284 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 (44284 hom., cov: 33)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.775
• Publications: 6 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]

LOC124901124 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 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.330+9348A>G		intron	N/A	NP_003305.1
	TTC1	NM_001282500.2		c.330+9348A>G		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.330+9348A>G		intron	N/A	ENSP00000231238.4
	TTC1	ENST00000522793.5	TSL:5	c.330+9348A>G		intron	N/A	ENSP00000429225.1
	TTC1	ENST00000682719.1		c.330+9348A>G		intron	N/A	ENSP00000507891.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115074 AN: 152032 Hom.: 44231 Cov.: 33

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.757 AC: 115185 AN: 152150 Hom.: 44284 Cov.: 33 AF XY: 0.758 AC XY: 56366 AN XY: 74376

African (AFR) AF: 0.898 AC: 37279 AN: 41536

American (AMR) AF: 0.771 AC: 11793 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2973 AN: 5178

South Asian (SAS) AF: 0.696 AC: 3352 AN: 4818

European-Finnish (FIN) AF: 0.728 AC: 7694 AN: 10574

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47503 AN: 67972

Other (OTH) AF: 0.761 AC: 1605 AN: 2108

Alfa AF: 0.719 Hom.: 126052

Bravo AF: 0.765

Asia WGS AF: 0.662 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.82
PhyloP100		0.78
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: rs10515804; hg19: chr5-159447213;