rs1106055

Positions:

• chr5-160064513-A-C
• chr5-160064513-A-G
• chr5-160064513-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003314.3(TTC1):​c.746-419A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC1	NM_003314.3	c.746-419A>C		intron_variant		ENST00000231238.10	NP_003305.1
TTC1	NM_001282500.2	c.746-419A>C		intron_variant			NP_001269429.1
PWWP2A	XM_011534424.4	c.1550-840T>G		intron_variant			XP_011532726.1
PWWP2A	XR_007058578.1	n.1612-840T>G		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>C		intron_variant		1	NM_003314.3	ENSP00000231238	P1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
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;