dbSNP rs376729010: TTC22:p.Gly390Asp (chr1-54782329-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001114108.2(TTC22):c.1169G>A(p.Gly390Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,535,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TTC22
NM_001114108.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC22	NM_001114108.2 link	c.1169G>A	p.Gly390Asp	missense_variant	Exon 6 of 7	ENST00000371276.9	NP_001107580.1	Q5TAA0-1
TTC22	XM_017001582.2 link	c.596G>A	p.Gly199Asp	missense_variant	Exon 6 of 7		XP_016857071.1
TTC22	XM_011541671.3 link	c.1021-550G>A		intron_variant	Intron 5 of 5		XP_011539973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC22	ENST00000371276.9 link	c.1169G>A	p.Gly390Asp	missense_variant	Exon 6 of 7	5	NM_001114108.2	ENSP00000360323.4		Q5TAA0-1
TTC22	ENST00000488771.1 link	n.2162G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000824

AC:

AN:

145646

AF XY:

0.0000646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000446

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

162

AN:

1383578

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

680862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30976

American (AMR)

AF:

0.0000600

AC:

AN:

33356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24408

East Asian (EAS)

AF:

0.0000283

AC:

AN:

35358

South Asian (SAS)

AF:

0.00

AC:

AN:

77986

European-Finnish (FIN)

AF:

0.0000206

AC:

AN:

48590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.000140

AC:

150

AN:

1070164

Other (OTH)

AF:

0.000140

AC:

AN:

57132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41468

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000583

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000402

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1169G>A (p.G390D) alteration is located in exon 6 (coding exon 6) of the TTC22 gene. This alteration results from a G to A substitution at nucleotide position 1169, causing the glycine (G) at amino acid position 390 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.1

PhyloP100

2.9

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.35

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Polyphen

0.62

Vest4

0.79

MVP

0.70

MPC

0.91

ClinPred

0.28

GERP RS

5.0

Varity_R

0.50

gMVP

0.87

Mutation Taster

=90/10

polymorphism

(source)

Splicing

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

Publications

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rs376729010

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over