Genetic Variant TTC22:p.Arg169Leu (chr1-54800658-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114108.2(TTC22):c.506G>T(p.Arg169Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: 7.1e-7 ( 0 hom. )

Consequence

TTC22
NM_001114108.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

0 publications found

Variant links:

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]

TTC22 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.069340944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2 link	c.506G>T	p.Arg169Leu	missense_variant	Exon 1 of 7	ENST00000371276.9	NP_001107580.1	Q5TAA0-1
TTC22	NM_017904.4 link	c.506G>T	p.Arg169Leu	missense_variant	Exon 1 of 6		NP_060374.2	Q5TAA0-2
TTC22	XM_011541671.3 link	c.506G>T	p.Arg169Leu	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 link	c.506G>T	p.Arg169Leu	missense_variant	Exon 1 of 7	5	NM_001114108.2	ENSP00000360323.4		Q5TAA0-1
TTC22	ENST00000371274.8 link	c.506G>T	p.Arg169Leu	missense_variant	Exon 1 of 6	2		ENSP00000360321.4		Q5TAA0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1401970

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30090

American (AMR)

AF:

0.00

AC:

AN:

37544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24754

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35962

South Asian (SAS)

AF:

0.00

AC:

AN:

80634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093088

Other (OTH)

AF:

0.00

AC:

AN:

58238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PhyloP100

1.3

PrimateAI

Uncertain

0.72

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.049

Sift

Benign

0.21

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0050

B;B

Vest4

0.40

MutPred

0.39

Loss of disorder (P = 0.061);Loss of disorder (P = 0.061);

MVP

0.12

MPC

0.37

ClinPred

0.54

GERP RS

3.4

Varity_R

0.22

gMVP

0.60

Mutation Taster

=83/17

polymorphism

(source)

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

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1-54800658-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over