5-160064513-A-G

Position:

• chr5-160064513-A-G

Variant summary

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

The NM_003314.3(TTC1):​c.746-419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,058 control chromosomes in the GnomAD database, including 26,569 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 0.59 (26569 hom., cov: 33)
• Consequence: TTC1 NM_003314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC1	NM_003314.3	c.746-419A>G		intron_variant		ENST00000231238.10	NP_003305.1
TTC1	NM_001282500.2	c.746-419A>G		intron_variant			NP_001269429.1
PWWP2A	XM_011534424.4	c.1550-840T>C		intron_variant			XP_011532726.1
PWWP2A	XR_007058578.1	n.1612-840T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC1	ENST00000231238.10	c.746-419A>G		intron_variant		1	NM_003314.3	ENSP00000231238	P1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89785 AN: 151940 Hom.: 26555 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.591 AC: 89832 AN: 152058 Hom.: 26569 Cov.: 33 AF XY: 0.595 AC XY: 44228 AN XY: 74326

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.567

Alfa AF: 0.598 Hom.: 45495

Bravo AF: 0.580

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.61

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: rs1106055; hg19: chr5-159491520; COSMIC: COSV51463676;