chr1-54800659-G-A

Variant names:

• chr1-54800659-G-A
• rs752247681
• NM_001114108.2:c.505C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001114108.2(TTC22):​c.505C>T​(p.Arg169Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TTC22 NM_001114108.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2735254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2	c.505C>T	p.Arg169Cys	missense_variant	Exon 1 of 7	ENST00000371276.9	NP_001107580.1
TTC22	NM_017904.4	c.505C>T	p.Arg169Cys	missense_variant	Exon 1 of 6		NP_060374.2
TTC22	XM_011541671.3	c.505C>T	p.Arg169Cys	missense_variant	Exon 1 of 6		XP_011539973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9	c.505C>T	p.Arg169Cys	missense_variant	Exon 1 of 7	5	NM_001114108.2	ENSP00000360323.4
TTC22	ENST00000371274.8	c.505C>T	p.Arg169Cys	missense_variant	Exon 1 of 6	2		ENSP00000360321.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397974 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 693232

African (AFR) AF: 0.00 AC: 0 AN: 29894

American (AMR) AF: 0.0000273 AC: 1 AN: 36626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24680

East Asian (EAS) AF: 0.00 AC: 0 AN: 35674

South Asian (SAS) AF: 0.00 AC: 0 AN: 80248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5456

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091310

Other (OTH) AF: 0.00 AC: 0 AN: 58088

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M;M
PhyloP100		3.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.63	N;N
REVEL	Benign	0.095
Sift	Uncertain	0.024	D;T
Sift4G	Uncertain	0.020	D;D
Polyphen		0.99	D;D
Vest4		0.42
MutPred		0.39		Loss of disorder (P = 0.031);Loss of disorder (P = 0.031);
MVP		0.28
MPC		0.82
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.19
gMVP		0.62
Mutation Taster		=86/14	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: rs752247681; hg19: chr1-55266332;