Genetic Variant TTC22:p.Met551Leu (chr1-54781302-T-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.1651A>T(p.Met551Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. M551V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

TTC22
NM_001114108.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.394

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=0.06951517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2 link	c.1651A>T	p.Met551Leu	missense_variant	Exon 7 of 7	ENST00000371276.9	NP_001107580.1	Q5TAA0-1
TTC22	XM_011541671.3 link	c.1498A>T	p.Met500Leu	missense_variant	Exon 6 of 6		XP_011539973.1
TTC22	XM_017001582.2 link	c.1078A>T	p.Met360Leu	missense_variant	Exon 7 of 7		XP_016857071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9 link	c.1651A>T	p.Met551Leu	missense_variant	Exon 7 of 7	5	NM_001114108.2	ENSP00000360323.4		Q5TAA0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000144

AC:

AN:

69450

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.57e-7

AC:

AN:

1320986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26322

American (AMR)

AF:

0.00

AC:

AN:

25202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22898

East Asian (EAS)

AF:

0.00

AC:

AN:

28702

South Asian (SAS)

AF:

0.0000137

AC:

AN:

72912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4554

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1052634

Other (OTH)

AF:

0.00

AC:

AN:

54742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

0.23

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0086

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.54

M_CAP

Benign

0.0049

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

0.39

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.47

REVEL

Benign

0.049

Sift

Benign

0.73

Sift4G

Benign

1.0

Polyphen

0.057

Vest4

0.22

MutPred

0.23

Loss of MoRF binding (P = 0.1068);

MVP

0.15

MPC

0.28

ClinPred

0.049

GERP RS

3.9

Varity_R

0.22

gMVP

0.42

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr1-54781302-T-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