rs41275305

chr5-160010614-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003314.3(TTC1):c.86C>G(p.Ala29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00801 in 1,614,118 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (100 hom.)
• Consequence: TTC1 NM_003314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023789108).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1760/152298) while in subpopulation AFR AF= 0.0242 (1007/41560). AF 95% confidence interval is 0.023. There are 23 homozygotes in gnomad4. There are 828 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC1	NM_003314.3	c.86C>G	p.Ala29Gly	missense_variant	2/8	ENST00000231238.10
TTC1	NM_001282500.2	c.86C>G	p.Ala29Gly	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC1	ENST00000231238.10	c.86C>G	p.Ala29Gly	missense_variant	2/8	1	NM_003314.3	P1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1751 AN: 152180 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00937 AC: 2356 AN: 251346 Hom.: 32 AF XY: 0.00964 AC XY: 1310 AN XY: 135854

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.00579

Gnomad ASJ exome AF: 0.0223

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0189

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00742

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.00765 AC: 11177 AN: 1461820 Hom.: 100 Cov.: 31 AF XY: 0.00790 AC XY: 5748 AN XY: 727208

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.00644

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0187

Gnomad4 FIN exome AF: 0.00221

Gnomad4 NFE exome AF: 0.00627

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0116 AC: 1760 AN: 152298 Hom.: 23 Cov.: 32 AF XY: 0.0111 AC XY: 828 AN XY: 74468

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00613

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00866 Hom.: 4

Bravo AF: 0.0126

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.0229 AC: 101

ESP6500EA AF: 0.00791 AC: 68

ExAC AF: 0.0102 AC: 1241

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.00840

EpiControl AF: 0.00789

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.9
Dann	Benign	0.93
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.084	N
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.012
Sift	Benign	0.089	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.020	B;B
Vest4		0.18
MPC		0.11
ClinPred		0.00067	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.063

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: rs41275305; hg19: chr5-159437621;