1-54787721-G-A

Variant names:

• chr1-54787721-G-A
• rs142120104
• NM_001114108.2:c.729C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001114108.2(TTC22):​c.729C>T​(p.Pro243Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,612,262 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (32 hom.)
• Consequence: TTC22 NM_001114108.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.870
• Publications: 2 publications found

Genes affected

TTC22 (HGNC:26067): (tetratricopeptide repeat domain 22) This gene encodes a protein with seven tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-54787721-G-A is Benign according to our data. Variant chr1-54787721-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.87 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2	c.729C>T	p.Pro243Pro	synonymous_variant	Exon 3 of 7	ENST00000371276.9	NP_001107580.1
TTC22	NM_017904.4	c.729C>T	p.Pro243Pro	synonymous_variant	Exon 3 of 6		NP_060374.2
TTC22	XM_011541671.3	c.729C>T	p.Pro243Pro	synonymous_variant	Exon 3 of 6		XP_011539973.1
TTC22	XM_017001582.2	c.156C>T	p.Pro52Pro	synonymous_variant	Exon 3 of 7		XP_016857071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9	c.729C>T	p.Pro243Pro	synonymous_variant	Exon 3 of 7	5	NM_001114108.2	ENSP00000360323.4

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 657 AN: 152188 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00654

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00494 AC: 1220 AN: 246782 AF XY: 0.00510

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00394

Gnomad ASJ exome AF: 0.0138

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.000795

Gnomad NFE exome AF: 0.00752

Gnomad OTH exome AF: 0.00448

GnomAD4 exome AF: 0.00584 AC: 8520 AN: 1459956 Hom.: 32 Cov.: 31 AF XY: 0.00579 AC XY: 4207 AN XY: 726122

African (AFR) AF: 0.000987 AC: 33 AN: 33446

American (AMR) AF: 0.00433 AC: 193 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 328 AN: 26054

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39618

South Asian (SAS) AF: 0.00128 AC: 110 AN: 85854

European-Finnish (FIN) AF: 0.00103 AC: 55 AN: 53206

Middle Eastern (MID) AF: 0.00973 AC: 56 AN: 5754

European-Non Finnish (NFE) AF: 0.00666 AC: 7399 AN: 1111170

Other (OTH) AF: 0.00573 AC: 345 AN: 60260

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152306 Hom.: 2 Cov.: 32 AF XY: 0.00404 AC XY: 301 AN XY: 74472

African (AFR) AF: 0.00152 AC: 63 AN: 41556

American (AMR) AF: 0.00523 AC: 80 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 68026

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00518 Hom.: 2

Bravo AF: 0.00488

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TTC22: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		0.87
PromoterAI		-0.0012	Neutral
Mutation Taster		=100/0	polymorphism

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: rs142120104; hg19: chr1-55253394;